Assessment of Primordial Radionuclides in Pakistani Red Bricks and Associated Radiation Doses

Specific activity of primordial radionuclides and associated radiation hazards due to 40K, 226Ra, and 232Th have been measured in backed red brick samples, collected from five highly populated areas of the North West Frontier Province of Pakistan. For the detection, analysis and data acquisition, a high purity germanium detector was used. Associated external doses were calculated using a Monte Carlo neutron photon transport code. A theoretical model to determine the gamma dose rate at 1 m height from the floor, made of bricks, was employed for the calculation of mass attenuation coefficient and self-absorption in the floor for the gamma energies of these radionuclides and their progeny. Monte Carlo simulation shows that in this study the floor, having more than an effective thickness of 15 cm, contributes very little to the external gamma dose rate. The values of the external dose rate and annual effective dose are found to be much lower than the world average as well as from other countries of the world.     

Enhancing proline-rich antimicrobial peptide action by homodimerization: influence of bifunctional linker

Antimicrobial peptides (AMPs) are host defense peptides, and unlike conventional antibiotics, they possess potent broad spectrum activities and, induce little or no antimicrobial resistance. They are attractive lead molecules for rational development to improve their therapeutic index. Our current studies examined dimerization of the de novo designed proline-rich AMP (PrAMP), Chex1-Arg20 hydrazide, via C-terminal thiol addition to a series of bifunctional benzene or phenyl tethers to determine the effect of orientation of the peptides and linker length on antimicrobial activity. Antibacterial assays confirmed that dimerization per se significantly enhances Chex1-Arg20 hydrazide action. Greatest advantage was conferred using perfluoroaromatic linkers (tetrafluorobenzene and octofluorobiphenyl) with the resulting dimeric peptides 6 and 7 exhibiting potent action against Gram-negative bacteria, especially the World Health Organization''s critical priority-listed multidrug-resistant (MDR)/extensively drug-resistant (XDR) Acinetobacter baumannii as well as preformed biofilms. Mode of action studies indicated these lead PrAMPs can interact with both outer and inner bacterial membranes to affect the membrane potential and stress response. Additionally, 6 and 7 possess potent immunomodulatory activity and neutralise inflammation via nitric oxide production in macrophages. Molecular dynamics simulations of adsorption and permeation mechanisms of the PrAMP on a mixed lipid membrane bilayer showed that a rigid, planar tethered dimer orientation, together with the presence of fluorine atoms that provide increased bacterial membrane interaction, is critical for enhanced dimer activity. These findings highlight the advantages of use of such bifunctional tethers to produce first-in-class, potent PrAMP dimers against MDR/XDR bacterial infections.

Homodimerization of a proline-rich antimicrobial peptide via bioconjugation to perfluoroaromatic linkers confers increased antimicrobial, antibiofilm and immunomodulatory activity. The dimers are promising new therapeutic leads against WHO priority multidrug resistant bacteria.     

Molecular Simulations and Drug Discovery of Adenosine Receptors

G protein-coupled receptors (GPCRs) represent the largest family of human membrane proteins. Four subtypes of adenosine receptors (ARs), the A₁AR, A_2AAR, A_2BAR and A₃AR, each with a unique pharmacological profile and distribution within the tissues in the human body, mediate many physiological functions and serve as critical drug targets for treating numerous human diseases including cancer, neuropathic pain, cardiac ischemia, stroke and diabetes. The A₁AR and A₃AR preferentially couple to the G_i/o proteins, while the A_2AAR and A_2BAR prefer coupling to the G_s proteins. Adenosine receptors were the first subclass of GPCRs that had experimental structures determined in complex with distinct G proteins. Here, we will review recent studies in molecular simulations and computer-aided drug discovery of the adenosine receptors and also highlight their future research opportunities.     

Observation of a registered phase in Cs/W(110)

RHEED and AES studies at room temperature have revealed a new metastable state of Cs ad-atoms on W(110) which are in registry at least along [1̄10] W. The ad-atom density in this state is 0.81 ± 0.03 ML, where 1 ML corresponds to the final density of Cs atoms in the saturated close packed hexagonal structure. This new structure has been observed as the final structure in dynamic deposition conditions, i.e. under the constant pressure of the Cs beam. The previously observed 1 ML structure arises when deposition and AES observations are alternated. The possibility that impurities provide the means of overcoming a nucleation barrier to this final structure is discussed.     

Copolymers from α-Pinene. 2. Cationic Copolymerization of Styrene and α-Pinene

A study of the copolymerization of α-pinene and styrene has been carried out at 10°C using anhydrous AlCl₃ as the initiator. It is found that styrene forms copolymer with α-pinene at all mono-meric ratios. A copolymer of 2320–3080 molecular weight is obtained. The softening range of the copolymer is 82 to 85°C. The copolymers are of commercial value.     

Microbial Proteins in Stomach Biopsies Associated with Gastritis,Ulcer, and Gastric Cancer

(1) Background: Gastric cancer (GC) is the fourth leading cause of cancer-related deaths worldwide. Helicobacter pylori infection is a major risk factor, but other microbial species may also be involved. In the context of an earlier proteomics study of serum and biopsies of patients with gastroduodenal diseases, we explored here a simplified microbiome in these biopsies (H. pylori, Acinetobacter baumannii, Escherichia coli, Fusobacterium nucleatum, Bacteroides fragilis) on the protein level. (2) Methods: A cohort of 75 patients was divided into groups with respect to the findings of the normal gastric mucosa (NGM) and gastroduodenal disorders such as gastritis, ulcer, and gastric cancer (GC). The H. pylori infection status was determined. The protein expression analysis of the biopsy samples was carried out using high-definition mass spectrometry of the tryptic digest (label-free data-independent quantification and statistical analysis). (3) Results: The total of 304 bacterial protein matches were detected based on two or more peptide hits. Significantly regulated microbial proteins like virulence factor type IV secretion system protein CagE from H. pylori were found with more abundance in gastritis than in GC or NGM. This finding could reflect the increased microbial involvement in mucosa inflammation in line with current hypotheses. Abundant proteins across species were heat shock proteins and elongation factors. (4) Conclusions: Next to the bulk of human proteins, a number of species-specific bacterial proteins were detected in stomach biopsies of patients with gastroduodenal diseases, some of which, like those expressed by the cag pathogenicity island, may provide gateways to disease prevention without antibacterial intervention in order to reduce antibiotic resistance.     

Analytical procedure for the determination of thorium, zinc and potassium in diet samples

Instrumental neutron activation analysis (INAA), and atomic absorption spectrometry (AAS) have been used for the determination of trace amounts of thorium, zinc, and potassium in diet samples. Interlaboratory comparison has been made. The z-scores show that INAA can be used to determine thorium and zinc whereas AAS can be employed to determine potassium in diet samples.     

Appraisal of radioactivity and associated radiation hazards in sand samples of four rivers of Punjab province,Pakistan

Natural and anthropogenic radioactivity of sand and water samples collected from the four big rivers of Punjab province, Pakistan, was measured using a high-purity germanium detector coupled with a high resolution multichannel analyser. The average concentration of the naturally occurring radionuclides ²²⁶Ra, ²³²Th and ⁴⁰K in all the sand samples from the rivers Jhelum, Chenab, Ravi and Indus was found to be 22±0.6, 36±1 and 287±10 Bq?kg ^?1, respectively, while the concentration of the anthropogenic radionuclide ¹³⁷Cs was found to be below the minimum detectable activity, i.e. ～ 1.2 Bq?kg ^?1. All the sand samples have Ra_eq concentrations lower than the limit of 370 Bq?kg ^?1. Indoor (H _in) and outdoor (H _out) radiation hazard indices were calculated for the samples to assess the radiation hazards arising due to the use of this sand in construction, and were found to be less than unity in the study area. Calculated values of the absorbed dose rate were less than the typical world average value of 59 nGy?h ^?1, and the annual effective dose rate was also less than the typical world value of 70 μSv, except in the Indus river, in which it is slightly higher then the world average. Results show that the measured values are comparable with other global radioactivity measurements. None of the studied riverbeds was considered a radiological hazard, and their sand can be safely used in construction.