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Over the last several decades, angiotensin-converting enzyme inhibitors (ACEIs) have been a staple in the treatment of hypertension and renovascular disorders in children. One of the ACEIs, captopril, is projected to have all the benefits of traditional vasodilators. However, conducting clinical trials for determining the pharmacokinetics (PK) of a drug is challenging, particularly in pediatrics. As a result, modeling and simulation methods have been developed to identify the safe and effective dosages of drugs. The physiologically based pharmacokinetic (PBPK) modeling is a well-established method that permits extrapolation from adult to juvenile populations. By using SIMCYP simulator, as a modeling platform, a previously developed PBPK drug-disease model of captopril was scaled to renally impaired pediatrics population for predicting captopril PK. The visual predictive checks, predicted/observed ratios (ratiopred/obs), and the average fold error of PK parameters were used for model evaluation. The model predictions were comparable with the reported PK data of captopril in mild and severe chronic kidney disease (CKD) patients, as the mean ratiopred/obs Cmax and AUC0−t were 1.44 (95% CI 1.07 − 1.80) and 1.26 (95% CI 0.93 − 1.59), respectively. The successfully developed captopril-CKD pediatric model can be used in suggesting drug dosing in children diagnosed with different stages of CKD.

Microfacies, palynofacies, and hydrocarbon source rock potential of Toarcian–Bathonian sediments of the Shinawari Formation are investigated in the Chichali Nala Section, Baroch Nala, Gulla Khel Nala, Surghar Range, and Askari Cement Factory Section, Nizampur Kala Chitta Range, Pakistan. The Shinawari Formation is dominated by a mix of limestone, sandstone, shale, marls, siltstone, and mudstone units with the association of laterite, hard grounds, coal layers, and coal disseminations. Microfacies analysis suggests that deposition of the Shinawari Formation occurred in peritidal lagoon, beach shoal to distal shelf setting. This interpretation is supported by sub-types of standard Tyson (in: Sedimentary organic matter, Springer, Berlin, 1995), palynofacies, which we have defined as palynofacies SFPF-A, attributed to a marginal dysoxic to an anoxic basinal setting, and palynofacies SFPF-B, deposited in heterolithic proximal platform settings. Some of the intervals have low ( $$\le 0.5\%$$ ) total organic carbon (TOC) values except for intervals with fair values (0.5–2.09%) in the Shinawari Formation in different stratigraphic sections. Despite some lower TOC values, and the presence of kerogen types III and II, spore colouration index of 5.0–8.0, thermal alteration index of 2–3+, and vitrinite reflectance (VR) of 1.16–1.35 indicate possible hydrocarbon source rock potential. The various geochemical plots obtained from TOC (%), VR and Rock-Eval pyrolysis data indicate that the Shinawari Formation specifies kerogen type III having Tmax ( $${}^{\circ }$$ C) range of 430–450 $${}^{\circ }$$ C and thermal maturity lies in the oil window.

In this study, the effect of change in electric and magnetic characteristics of Al–Cu–Fe quasicrystals (QCs), by de-alloying of Al from the surface, was investigated. Dissolution of Al was carried out in NaOH aqueous solution which did not change the icosahedral structure of Al–Cu–Fe; however, it changed the non-magnetic nature of Al–Cu–Fe QCs into the ferromagnetic one. This has never been reported in previous studies on Al–Cu–Fe QCs. The ferromagnetic characteristics of icosahedral Al–Cu–Fe QCs powder (at room temperature and 5 K) were studied in detail using vibrating sample magnetometer (VSM). For the first time, it is reported that the value of susceptibility (χm) of Al–Cu–Fe QCs was in the order of 103 which is considerably greater then χm value of diamagnetic and paramagnetic materials. The VSM data indicate that approximately ≈ 1.5% of the total Fe atoms in icosahedral Al–Cu–Fe QC contribute to magnetism and most of which comes from the leached icosahedral surface. Further, Mossbauer spectroscopy (MS) results of Al–Cu–Fe QC powder samples confirm the presence of high spin Fe3+ ionic state. Linear lines of current–voltage (I–V) graph indicate the Ohmic behavior of samples before and after leaching process.

In this study, for the first time, antimicrobial properties of Al–Cu–Fe, Al–Cu–Fe–B and Al–Cu–Fe–Co quasicrystal powders were investigated in the leached and un-leached condition against Gram-negative (E. aerogenes, K. pneumoniae) and Gram-positive (B. cereus, K. rosea) bacterial environment. Leaching of the powders in 10 M NaOH aqueous solution resulted in the enrichment of Cu and Fe at the surface. Consequently, bacterial activities in the vicinity of the leached quasicrystal powders were inhibited, indicating good antimicrobial characteristics of the leached powders. All the three leached powder samples exhibited antimicrobial activities with a varying degree. From the diameter of inhibition zone, it was deduced that E. aerogenes are the most susceptible against the leached powders. The leached Al–Cu–Fe–B and Al–Cu–Fe–Co quasicrystal powders showed nanostructured features on the outer surface. During leaching, the icosahedral structure was retained in all the samples.

Hybrid aluminum matrix composites containing particles of boron carbide and quasicrystals were manufactured to explore the combined effect of reinforcements on microstructural evolution and mechanical performance of the composites. The particles were incorporated at a loading of 6 wt% each making a total of 12 wt% reinforcement in pure aluminum. For comparison, two composites containing individually reinforced 12 wt% particles were also prepared along with a reference specimen of pure aluminum. Ball milling technique was employed to mix the composite constituents. The green bodies of composite powders were prepared by uniaxial pressing at room temperature followed by consolidation by pressureless sintering under inert atmosphere. The microstructural characterization was performed using scanning electron microscopy while phase identification was carried out by X-ray diffraction. The mechanical characterization was performed by Vickers hardness and compression tests. Hybrid composites showed increased compressive properties while the composites containing solely quasicrystals demonstrated improved hardness. The increase in mechanical performance was related to the microstructural evolution due to the presence and uniform dispersion of binary particles.

The present research is focused on studying the evolution of microstructure and texture of a magnesium based alloy with the target composition Mg–3Al–1Zn–(0.5AgIn). Three samples A, B, and C were warm rolled at 300 °C to a cumulative reduction of 33% in 1, 2, and 8 passes, respectively. The optical microstructures and scanning electron microscopy (SEM) results revealed that sample A possessed more dynamic recrystallization (DRX) as compared to samples B and C. A split of basal pole from normal direction (ND) toward transverse direction (TD) was observed for sample A. However, as the number of passes was increased, the basal pole split was converted into a single peak for samples B and C. The basal intensity of sample C became almost double than that of sample A. It was concluded that a higher reduction per pass resulted in a larger volume fraction of DRXed grains and a weaker basal texture.

1. In the first sentence of the Abstract, “Charrat” should be changed to “Makarwal.” The sentence should now read “The Lockhart Formation from a major carbonate unit of the Paleocene Makarwal Group in Upper Indus Basin, Pakistan represents a larger foraminiferal–algal build up deposited in a cyclic sequence of the carbonate ramp.” 2. The texts “(see plate-xx for top most bed of Hangu Formation)”, which is found at the bottom part of the Figure 3 should not be captured.

In the present study the comet assay was performed in buccal epithelial cells to evaluate DNA damage among pan masala or gutkha chewers and smokers. The assay is a rapid, suitable and sensitive method for detecting various forms of DNA damage at individual cell level. The study comprises 300 individuals of which 50 individuals were gutkha chewers along with smoking, 50 individuals were pan masala chewers along with smoking, 50 individuals were gutkha chewers, 50 individuals were pan masala chewers, 50 individuals were smokers and 50 individuals were non-users (control) or not having any addiction. Comet tail length was observed to measure the extent of DNA damage. In all groups a significant increase in the tail length was observed as compared to the non-users (control). The highest tail length was observed among gutkha chewers along with smoking (36.9 ± 3.60). The results of the present study suggest that the panmasala and gutkha are genotoxic agents and induce DNA damage. Keywords : Comet assay; DNA damage; Gutkha; Pan masala; Buccal epithelial cells

The Lockhart Formation from a major carbonate unit of the Paleocene Charrat Group in Upper Indus Basin, Pakistan represents a larger foraminiferal–algal build up deposited in a cyclic sequence of the carbonate ramp. The foraminiferal–algal assemblages of the Lockhart Formation are correlated here to larger foraminiferal biostratigraphic zone, i.e. Shallow Benthic Zone (SBZ3) of the Thanetian Age. Inner ramp lagoon, shoal and fore shoal open marine are three main facies associations represented by wackstone and packstone foraminiferal–algal deposits. These facies are present in a cyclic order and displayed a retrograding carbonate ramp indicating the Thanetian transgressive deposits associated with eustatic sea level rise. The correlation of the microfacies of the Lockhart Formation (Upper Indus Basin) and facies of the Dungan Formation (Lower Indus Basin) provide detailed configuration of the depositional setting of the Indus Basin during the time interval represented by the Thanetian Zone SBZ3.

Out of the numerous potential petroleum source rocks, present in the Lower Indus Basin, Sembar Formation is the most promising rock unit. One-dimensional maturity modeling of source rocks in Lower Indus Basin is conducted to find out the lateral and vertical extents of maturity levels of Sembar Formation. This study is also aimed to infer the extent of petroleum generation in the region. The study is based on one-dimensional basin modeling (maturity modeling) of 22 main exploration wells, drilled in the region. Stratigraphic input to model includes thickness, formation tops, ages of deposition and lithology, age and amounts of erosion, and ages of non-depositional events. Isopach map of Sembar Formation demonstrates the lateral and vertical extents of the formation, whereas temperature and vitrinite reflectance (R o) contour maps indicate its maturity levels in different parts of the study area. It is inferred that the thickness of the overlying rock units (overburden) control the maturity level of the Sembar Formation. It may be noticed that the findings of this study are fully in conformity with the ground realities of the Lower Indus Basin. Discovery patterns and the lateral distribution of various types of hydrocarbons (such as oil, condensate, and dry gas) in the region coincide with the modeling results of the study, as can be seen from the burial history diagrams of the 12 wells. The study shows that Sembar Formation is mature enough to be considered as conventional petroleum source rock or can be exploit as unconventional shale gas/oil source.