Genome-wide CRISPR Screens in T Helper Cells Reveal Pervasive Crosstalk between Activation and Differentiation.

T helper type 2 (Th2) cells are important regulators of mammalian adaptive immunity and have relevance for infection, autoimmunity, and tumor immunology. Using a newly developed, genome-wide retroviral CRISPR knockout (KO) library, combined with RNA-seq, ATAC-seq, and ChIP-seq, we have dissected the regulatory circuitry governing activation and differentiation of these cells. Our experiments distinguish cell activation versus differentiation in a quantitative framework. We demonstrate that these two processes are tightly coupled and are jointly controlled by many transcription factors, metabolic genes, and cytokine/receptor pairs. There are only a small number of genes regulating differentiation without any role in activation. By combining biochemical and genetic data, we provide an atlas for Th2 differentiation, validating known regulators and identifying factors, such as Pparg and Bhlhe40, as part of the core regulatory network governing Th2 helper cell fates.

Loss of Function Variants in the XPC Causes Severe Xeroderma Pigmentosum in Three Large Consanguineous Families.

BACKGROUND: Xeroderma pigmentosum (XP) is a rare recessively inherited disorder that presents clinical and genetic heterogeneity. Mutations in eight genes, of which seven are involved in nucleotide excision repair (NER) pathway have been reported to cause the XP. METHODS AND RESULTS: Three large consanguineous families of Pakistani origin displaying typical clinical hallmarks of XP were evaluated at clinical and molecular level. Homozygosity mapping using microsatellite markers established linkage of the families to XPC gene on chromosome 3p25.1. Sanger sequencing of the XPC gene identified a novel homozygous single bp deletion [NM_004628.5; c.1934del; p.(Pro645Leufs*5)] and two previously reported mutations that included a nonsense [c.1243 C>T; p.(Arg415*)] and a splice acceptor site (c.2251-1 G>C), all segregating with the disease phenotypes in the families. CONCLUSION: This report has extended the spectrum of mutations in the XPC gene and will also facilitate in diagnosis of XP and counselling of families inheriting it, which is the only inevitable tool for preventing the disease occurrence in future generations.

A Review of Multi-Modal Learning from the Text-Guided Visual Processing Viewpoint.

For decades, co-relating different data domains to attain the maximum potential of machines has driven research, especially in neural networks. Similarly, text and visual data (images and videos) are two distinct data domains with extensive research in the past. Recently, using natural language to process 2D or 3D images and videos with the immense power of neural nets has witnessed a promising future. Despite the diverse range of remarkable work in this field, notably in the past few years, rapid improvements have also solved future challenges for researchers. Moreover, the connection between these two domains is mainly subjected to GAN, thus limiting the horizons of this field. This review analyzes Text-to-Image (T2I) synthesis as a broader picture, Text-guided Visual-output (T2Vo), with the primary goal being to highlight the gaps by proposing a more comprehensive taxonomy. We broadly categorize text-guided visual output into three main divisions and meaningful subdivisions by critically examining an extensive body of literature from top-tier computer vision venues and closely related fields, such as machine learning and human-computer interaction, aiming at state-of-the-art models with a comparative analysis. This study successively follows previous surveys on T2I, adding value by analogously evaluating the diverse range of existing methods, including different generative models, several types of visual output, critical examination of various approaches, and highlighting the shortcomings, suggesting the future direction of research.

Detection of aflatoxin M1 by fiber cavity attenuated phase shift spectroscopy.

Aflatoxin M1 (AFM1) is a carcinogenic compound commonly found in milk in excess of the WHO permissible limit, especially in developing countries. Currently, state-of-the-art tests for detecting AFM1 in milk include chromatographic systems and enzyme-linked-immunosorbent assays. Although these tests provide fair accuracy and sensitivity, they require trained laboratory personnel, expensive infrastructure, and many hours to produce final results. Optical sensors leveraging spectroscopy have a tremendous potential of providing an accurate, real-time, and specialist-free AFM1 detector. Despite this, AFM1 sensing demonstrations using optical spectroscopy are still immature. Here, we demonstrate an optical sensor that employs the principle of cavity attenuated phase shift spectroscopy in optical fiber cavities for rapid AFM1 detection in aqueous solutions at 1550 nm. The sensor constitutes a cavity built by two fiber Bragg gratings. We splice a tapered fiber of < 10 µm waist inside the cavity as a sensing head. For ensuring specific binding of AFM1 in a solution, the tapered fiber is functionalized with DNA aptamers followed by validation of the conjugation via FTIR, TGA, and EDX analyses. We then detect AFM1 in a solution by measuring the phase shift between a sinusoidally modulated laser input and the sensor output at resonant frequencies of the cavity. Our results show that the sensor has the detection limit of 20 ng/L (20 ppt), which is well below both the U.S. and the European safety regulations. We anticipate that the present work will lead towards a rapid and accurate AFM1 sensor, especially for low-resource settings.

The role of Interleukin-32 in autoimmunity.

Interleukin-32 (IL-32) is a pro-inflammatory cytokine that induces other cytokines involved in inflammation, including tumour necrosis factor (TNF)-α, IL-6 and IL-1ß. Recent evidence suggests that IL-32 has a crucial role in host defence against pathogens, as well as in the pathogenesis of chronic inflammation. Abnormal IL-32 expression has been linked to several autoimmune diseases, such as rheumatoid arthritis and inflammatory bowel diseases, and a recent study suggested the importance of IL-32 in the pathogenesis of type 1 diabetes. However, despite accumulating evidence, many molecular characteristics of this cytokine, including the secretory route and the receptor for IL-32, remain largely unknown. In addition, the IL-32 gene is found in higher mammals but not in rodents. In this review, we outline the current knowledge of IL-32 biological functions, properties, and its role in autoimmune diseases. We particularly highlight the role of IL-32 in rheumatoid arthritis and type 1 diabetes.

Green synthesis, in vivo and in vitro pharmacological studies of Tamarindus indica based gold nanoparticles.

The current investigation aims to synthesize gold nanoparticles (AuNPs) from aqueous extract of Tamarindus indica and to evaluate the in vitro anti-bacterial and in vivo sedative and anelgescic activities of crude extract as well as synthesized AuNPs. Several methods have been reported to synthesize AuNPs; however, most of them were not ecofriendly. In the present study, the green synthesis of AuNPs has been carried out. Using the green synthesis method, AuNPs of T. indica were synthesized at room temperature (25 °C) by mixing 5 mL of HAuCl4 (1 mM) with 1 mL of T. indica seed extract solution. This extract solution was prepared by taking 5 gm dry seeds in 100 mL of double deionized water with continuous stirring for up to 24 h at 80 °C. The stability of AuNPs was confirmed with the help of relevant experimental techniques including ultraviolet-visible (UV/Vis) showing maximum absorbance at 535-540 nm, Fourier transform infrared showing a broad signal at 3464 cm-1 which can be attributed to either amide or hydroxyl functionalities and atomic force microscopy analysis showed that the biomaterial surrounding AuNPs was agglomerated which proves the formation of discrete nanostructutres. These AuNPs have been evaluated for their antibacterial potential. The results revealed good antibacterial activity of the samples against. Klebsiella pneumonia, Bacillus subtilis and Staphylococcus epidermidis with 10-12 mm zone of inhibition range. The AuNPs were also found stable at high temperature, over a range of pH and in 1 mM salt solution. Moreover, the crude extract and respective AuNPs also exhibited interesting sedative and analgesic activities. Hence, we focused on phytochemicals-mediated synthesis of AuNPs considered as greatest attention in the treatment of anti-bacterial, analgesic, and sedative.

Assessment of Drinking Water Sources for Water Quality, Human Health Risks, and Pollution Sources: A Case Study of the District Bajaur, Pakistan.

The focus of the present study was to assess the quality of different drinking water sources, impacts of poor water quality on human health, and to apportion pollution source(s) of the district Bajaur, Pakistan. Drinking water samples (n = 331) were randomly collected from springs, hand pumps, open wells, and tube wells and analyzed for physicochemical parameters including toxic elements, and bacteriological contamination (i.e., Escherichia coli). Furthermore, a questionnaire survey was conducted to record the cases of waterborne diseases in the study area. The results showed that total suspended solids and bacteriological contamination exceeded the permissible limits of the WHO in all four of the water sources. Among the potentially toxic elements, Cd, Pb, and Mn were above the permissible limits of the WHO in some samples. The hazard index for spring water was found to exceed the toxicity level (i.e., HI > 1) set by US EPA for both adults and children, while the sources from hand pumps, open wells, and tube wells were within the safe limit. The order for the overall safety level for water quality in the study area was tube wells > open wells > hand pumps > springs. The pollution source apportionment statistics revealed that both geogenic and anthropogenic activities are the sources of drinking water contamination. The results of the questionnaire survey indicated that reports of waterborne diseases were highest in respondents who took their drinking water from springs, whereas reports of diseases were moderate in respondents taking their water from open wells and hand pumps and lowest in respondents taking their water from tube wells. Based on the findings of the study, the tube well source of water is recommended for drinking water purposes.

Hepatoprotective effects of melatonin and celecoxib against ethanol-induced hepatotoxicity in rats.

Objectives: Several studies demonstrated the antioxidant and anti-inflammatory role of melatonin and celecoxib. This study is designed to explore the underlying mechanism of hepatoprotective effects of melatonin and celecoxib against ethanol-induced hepatotoxicity by morphological, and biochemical approaches.Materials and methods: Adult male rats were divided into five groups: saline, ethanol, melatonin, and celecoxib were administered for 11 consecutive days after ethanol injection. Biochemical analyses were performed for the determination of glutathione (GSH), glutathione S-transferase (GST), and inducible nitric oxide (iNOS). Immunohistochemistry was performed to determine the level of different inflammatory markers.Results: Histopathological results showed that ethanol-induced marked hepatic injury leads to cloudy swelling, hydropic degeneration, apoptosis, and focal necrosis in all hepatic zones. Biochemical analysis revealed significant increases in serum transaminases and alkaline phosphatase in the ethanol group. Oxidative stress associated with attenuated antioxidant enzymes was also spotted in the ethanol group, as ethanol down-regulated GSH, GST, and upregulated NO. Additionally, ethanol increased the activation and the expression of tumor necrotic factor (TNF-α), p-NFKB, and COX2. Finally, hepatic cellular apoptosis was clearly obvious in ethanol intoxicated animals using activated JNK staining.Conclusion: These results provided pieces of evidence that the hepatoprotective effect of melatonin and celecoxib is possibly mediated through the modulation of JNK and TNF-α signaling pathways with subsequent suppression of inflammatory and apoptotic processes.

Time-resolved transcriptome and proteome landscape of human regulatory T cell (Treg) differentiation reveals novel regulators of FOXP3.

BACKGROUND: Regulatory T cells (Tregs) expressing the transcription factor FOXP3 are crucial mediators of self-tolerance, preventing autoimmune diseases but possibly hampering tumor rejection. Clinical manipulation of Tregs is of great interest, and first-in-man trials of Treg transfer have achieved promising outcomes. Yet, the mechanisms governing induced Treg (iTreg) differentiation and the regulation of FOXP3 are incompletely understood. RESULTS: To gain a comprehensive and unbiased molecular understanding of FOXP3 induction, we performed time-series RNA sequencing (RNA-Seq) and proteomics profiling on the same samples during human iTreg differentiation. To enable the broad analysis of universal FOXP3-inducing pathways, we used five differentiation protocols in parallel. Integrative analysis of the transcriptome and proteome confirmed involvement of specific molecular processes, as well as overlap of a novel iTreg subnetwork with known Treg regulators and autoimmunity-associated genes. Importantly, we propose 37 novel molecules putatively involved in iTreg differentiation. Their relevance was validated by a targeted shRNA screen confirming a functional role in FOXP3 induction, discriminant analyses classifying iTregs accordingly, and comparable expression in an independent novel iTreg RNA-Seq dataset. CONCLUSION: The data generated by this novel approach facilitates understanding of the molecular mechanisms underlying iTreg generation as well as of the concomitant changes in the transcriptome and proteome. Our results provide a reference map exploitable for future discovery of markers and drug candidates governing control of Tregs, which has important implications for the treatment of cancer, autoimmune, and inflammatory diseases.

Rifampicin resistance mutations in the 81 bp RRDR of rpoB gene in Mycobacterium tuberculosis clinical isolates using Xpert MTB/RIF in Khyber Pakhtunkhwa, Pakistan: a retrospective study.

BACKGROUND: Multi-drug resistant tuberculosis (MDR-TB) is a major public health problem especially in developing countries. World Health Organization (WHO) recommends use of Xpert MTB/RIF assay to simultaneously detecting Mycobacterium tuberculosis (MTB) and rifampicin (RIF) resistance. The primary objective of this study was to determine the frequency of MDR-TB in patients suspected to have drug resistance in Khyber Pakhtunkhwa. The frequency of probes for various rpoB gene mutations using Xpert MTB/RIF assay within 81 bp RRDR (Rifampicin Resistance Determining Region) was the secondary objective. METHODS: A total of 2391 specimens, received at Programmatic Management of Drug Resistant TB (PMDT) Unit, Lady Reading Hospital (LRH) Peshawar, Pakistan, between October 2011 and December 2014, were analyzed by Xpert MTB/RIF test. MTB positive with rifampicin resistance were further analyzed to first line anti-mycobacterial drug susceptibility testing (DST) using middle brook 7H10 medium. The data was analyzed using statistical software; SPSS version 18. RESULTS: Out of 2391 specimens, 1408 (59 %) were found positive for MTB and among them, 408 (29 %) showed rifampicin-resistance with four different rpoB gene mutations within 81 bp RRDR. The frequency of various probes among RIF-resistant isolates was observed as: probe E, in 314 out of 408 isolates; B, 44 out of 408; A, 5 out of 408; D, 34 out of 408; and probe C was observed among 6 out of 408 RIF-resistant isolates. The probe A&B and E&D mutation combination was found in only 1 isolate in each case, while B&D mutation combination was detected among 3 out of 408 RIF-resistant isolates. CONCLUSIONS: Hence, it is concluded from our study on a selected population, 29 % of patients had MDR-TB. Probe E related mutations (also known as codon 531and 533) were the most common rpoB genetic mutation [314 (77 %)], acknowledged by Xpert MTB/RIF assay. Least mutation was detected within the sequence 511 (1.2 %).

Integrating the ESM usage and work engagement for employee agility performance: based on regulatory focus theory.

This present research aims to clarify the intricate conjunction of enterprise social media (ESM) utilization and employee agility with a main focus on uncovering the underlying mechanisms that work through the mediating influence of work engagement and the moderating influence of regulatory focus. Drawing upon regularity focus theory, 353 Chinese samples of ESM users in organizational contexts are analyzed using SPSS 23.0. The empirical findings substantiate a robust and significant positive linkage between ESM usage and worker agility. Further reinforcing the model, the mediating role of work engagement is established as it channels the impact of ESM usage on worker agility. Turning to the moderating effects, the study unveils the differential impact of prevention focus and promotion focus, wherein individuals with a lower prevention focus exhibit a more pronounced positive linkage between ESM usage and worker agility. Similarly, individuals with a higher promotion focus demonstrate a heightened positive association between ESM usage and worker agility. By comprehensively inspecting the intricate dynamics of ESM usage, work engagement, and regulatory focus, this study enhances our theoretical understanding of how these factors synergistically shape employee agility, ultimately furnishing organizations with invaluable insights to foster and cultivate an agile workforce.

Highly integrable planar-structured printed circularly polarized antenna for emerging wideband internet of things applications in the millimeter-wave band.

This paper proposes a numerically and experimentally validated printed wideband antenna with a planar geometry for Internet of Things (IoT) applications. This design tackles the challenges associated with deploying IoT sensors in remote areas or across extensive geographical regions. The proposed design exploits a coplanar-waveguide-fed modified microstrip line monopole for excitation of circularly polarized waves radiating in the broadside direction. The primary design is based on perturbations of the microstrip line protracted from a grounded coplanar waveguide. The capacitively coupled short rectangular stubs are periodically inserted alternately and excited asymmetrically on each side of the microstrip line parallel to the direction of the electric field vector. The sequential phase excitation of the periodic stubs generates a rectangular-cascaded electric field, which suppresses the stop band at the open end. As a result, the antenna radiates in the broadside direction. The impedance bandwidth of the antenna exceeds 8 GHz in the 28 GHz mm-wave band, i.e., it ranged from 25 to 33.5 GHz. Additionally, an axial ratio below 3 dB is achieved within the operating band from 26 to 33.5 GHz with the alterations of the surface current using straightforward topological adjustments of the physical parameters. The average in-band realized gain of the antenna is 10 dBic when measured in the broadside direction. These results indicate that the proposed design has the potential to improve the connectivity between IoT devices and the constantly varying orientation of satellites by mitigating the polarization mismatch.

Expedited re-design of multi-band passive microwave circuits using orthogonal scaling directions and gradient-based tuning.

Geometry scaling of microwave circuits is an essential but challenging task. In particular, the employment of a given passive structure in a different application area often requires re-adjustment of the operating frequencies/bands while maintaining top performance. Achieving this necessitates the utilization of numerical optimization methods. Nonetheless, if the intended frequencies are distant from the ones at the starting point, local search procedures tend to fail, whereas global search algorithms are computationally expensive. As recently demonstrated, a combination of large-scale concurrent geometry parameter scaling with intermittent local tuning allows for dependable re-design of high-frequency circuits at low CPU costs. Unfortunately, the procedure is only applicable to single-band structures due to synchronized modifications of all operating bands under scaling. This article discusses a novel procedure that leverages a similar overall concept, but allows for independent control of all center frequencies. To achieve this goal, an automated decision-making procedure is developed in which a set of orthogonal scaling directions are determined based on their effect on individual circuit bands, and using auxiliary optimization sub-problems. The scaling range is then automatically computed by solving an appropriately-defined least-square design relocation problem. The methodology introduced in the work is illustrated using two planar passive devices. In both cases, wide-range operating frequency re-design has been demonstrated and favorably compared to conventional gradient-based tuning. Furthermore, the presented procedure has been shown to be computationally efficient. It is also easy to implement and integrate with a variety of gradient-based optimization procedures of a descent type.

Lipoarabinomannan-based tuberculosis diagnosis using a fiber cavity ring down biosensor.

Despite existing for millennia, tuberculosis (TB) remains a persistent global health challenge. A significant obstacle in controlling TB spread is the need for a rapid, portable, sensitive, and accurate diagnostic test. Currently, sputum culture stands as a benchmark test for TB diagnosis. Although highly reliable, it necessitates advanced laboratory facilities and involves considerable testing time. In this context, we present a rapid, portable, and cost-effective optical fiber sensor designed to measure lipoarabinomannan (LAM), a TB biomarker found in patients' urine samples. Our sensing approach is based on the applications of phase shift-cavity ringdown spectroscopy (PS-CRDS) to an optical fiber cavity created by two fiber Bragg gratings. A tapered fiber is spliced inside the optical cavity to serve as the sensing head. We functionalize the tapered fiber surface with anti-LAM antigen CS-35 through a unique chemistry, creating a strong affinity for LAM molecules. We measure the phase difference between the cavity transmission and the reference modulating signal at the cavity output. The measured phase is directly proportional to the injected LAM concentrations in aqueous solutions over the sensing head. Our demonstrated sensor provides a detection limit of 10 pg/mL and a sensitivity of 0.026°/pg/mL. This sensor holds promise for numerous applications in the healthcare sector, particularly in low-resource settings.

Frequency and Risk Factors of Tracheomalacia in Patients Undergoing Thyroidectomy.

It was a descriptive cross-sectional study to determine the frequency and risk factors of tracheomalacia in patients undergoing thyroidectomy. One hundred and forty-nine patients underwent thyroidectomy at MTI-Khyber Teaching Hospital Peshawar between 1st January 2021 and 1st March 2022. The frequency of post-thyroidectomy tracheomalacia and possible associated factors were determined. The inclusion criteria were patients of either gender, between 18 to 70 years fulfilling criteria of clinically diagnosed cases of thyroid disorders who underwent subtotal, hemi, near or total thyroidectomy for their respective thyroid diseases. Post-thyroidectomy tracheomalacia was recorded in 18 patients (12.1%): Seventeen patients were aged less than 30 (p-value 0.038) and 14 (77.8%) patients had a duration of surgery > three hours (p-value <0.001). Young female patients with multinodular goitre who had a longer duration of surgery developed post-thyroidectomy tracheomalacia more frequently. Hence, the incidence of post-thyroidectomy tracheomalacia can be markedly reduced with proper preoperative assessment and postoperative measures. Key Words: Thyroid gland, Thyroid disorders, Tracheomalacia, Thyroidectomy.

Comparison of the Latarjet Procedure With the Modified Putti-Platt Surgery for Recurrent Anterior Shoulder Dislocation With Respect to Functional Outcome.

Introduction Shoulder dislocation is the most common injury encountered in orthopedic outpatient department. The choice of procedure depends on the expertise of surgeons. The objective of this study was to compare the Latarjet procedure with the modified Putti-Platt surgery for recurrent anterior shoulder dislocation in terms of functional outcomes. Materials and methods A quasi-experimental study evaluated 60 patients with recurrent anterior shoulder instability. Patients were assigned to either Latarjet or modified Putti-Platt surgery. Functional outcomes were assessed at six months using the Constant-Murley shoulder score. Results This study encompassed 60 patients (mean age: 23.93±5.88 years) undergoing shoulder procedures. Functional outcomes exhibited a majority of 55% excellent, 35% good, 6.7% fair, and 3.3% poor outcomes. No significant differences in functional outcomes were found between the procedures. Conclusion Both procedures may be viable options for recurrent shoulder instability. The choice may depend on patient factors and surgeon preference. Further research is needed to refine techniques and identify ideal candidates.

Comparison of Partial Meniscectomy With Meniscal Repair With Respect to Functional Outcome.

Introduction Meniscus tear is a commonly encountered sports-related injury requiring surgical intervention due to knee mobility dysfunction and discomfort. Previously, it has been thought that these are non-functional vestigial structures and they used to be excised commonly. Recent studies have shown that meniscal repair gives superior results when compared with partial meniscectomy. Methods This quasi-experimental study was conducted at the Orthopedics Department, Khyber Teaching Hospital, Peshawar, Pakistan. A total of 92 patients of both genders with meniscal injuries were included. Forty-six of them underwent meniscal repair (Group A), and 46 underwent partial meniscectomy (Group B). Functional outcome was noted after 12 weeks and recorded. Results The age range was from 18 to 50 years with a mean of 28.630±6.64 years in Group A and 29.630±8.12 years in Group B. Functional outcome was excellent in 44 (95.7%) patients who underwent meniscal repair as compared to 23 (50%) patients who underwent partial meniscectomy (P= 0.000). Conclusion It is concluded that meniscal repair should be pursued over partial meniscectomy when surgically treating meniscal tears.

In vivo analgesic, anti-inflammatory and molecular docking studies of S-naproxen derivatives.

In the current studies two naproxen derivatives (NPD) were evaluated for analgesic and anti-inflammatory properties. The acetic acid and hot plate animal models were used to screen the compounds for analgesic potential. While the anti-inflammatory potential was evaluated through animal paw edema, induced by several inflammatory mediators (carrageenan, bradykinin, and prostaglandin E2), the xylene-induced ear edema was also used as an inflammatory model. Both NPDs showed significant (p < 0.001) antinociceptive effects in the acetic acid-induced writhing paradigm. In the case of the hot plate, the NPD 1 at the tested dose of 5 mg/kg enhanced the latency time after 60 min of injection, which remained significant (p < 0.001) up to the end of the experiment duration. The maximum percent inhibition of NPD 1 was 87.53. The naloxone injection significantly lowered the latency time of NPD 1 as compared to NPD 2. Regarding the anti-inflammatory effect, both of the tested NPDs demonstrated a significant reduction in paw edema against various inflammatory mediators, as mentioned above; however, the anti-inflammatory effect of NPD 1 was better. The maximal percent inhibition by NPD 1 and 2 was 43.24 (after 60 min) and 45.93 (after 90 min). A considerable effect also resulted from xylene-induced ere edema. Further, a molecular docking study was carried out to investigate the binding modes of the NPD. The docking analysis revealed that the NPD significantly interacted with the COX2 enzyme. Furthermore, molecular dynamics simulation was carried out for the docked complexes. The MD simulation analysis revealed the high stability of the two naproxen derivatives.

Quantification of toxic heavy metals, trace elements and essential minerals contents in traditional herbal medicines commonly utilized in Khyber Pakhtunkhwa, Pakistan.

Traditional herbal medicines and health supplements have been empirically used to treat various disorders but most of them are not standardized and have not been experimentally validated for safety and efficacy. In the present study, various dosage forms of traditional herbal medicines prescribed for specific diseases were collected from local practitioners at different districts of Khyber Pakhtunkhwa, Pakistan. The collected samples were analyzed for heavy metal, trace elements, and minerals using atomic absorption spectroscopy. All the tested samples contained heavy metals, trace elements and minerals in different concentrations. All the samples were tested positive for the presence of toxic heavy metals such as arsenic (As), cadmium (Cd) and lead (Pb). The trace elements like cobalt (Co), iron (Fe), zinc (Zn) and chromium (Cr) were also detected in acceptable range. Similarly, the samples analyzed were rich in some of the essential minerals such as sodium (Na), magnesium (Mg) and calcium (Ca) which are necessary for the proper functioning of the body. The hazard quotient (HQ) values were measured for toxic heavy metals to determine their safe ranges for human body. The HQ values were above the permissible range for arsenic (As) in all detected samples while for cadmium (Cd) and lead (Pb), the values ware above in 50 % of the analyzed samples. The detection of toxic metals and their HQ values beyond the permissible limits in different dosage forms raised questions about their quality. This study suggests that evaluation of traditional herbal remedies for the metals contents and their standardization are strongly recommended for quality assurance and protection of public health.

Reduced-cost microwave modeling using constrained domains and dimensionality reduction.

Development of modern microwave devices largely exploits full-wave electromagnetic (EM) simulations. Yet, simulation-driven design may be problematic due to the incurred CPU expenses. Addressing the high-cost issues stimulated the development of surrogate modeling methods. Among them, data-driven techniques seem to be the most widespread owing to their flexibility and accessibility. Nonetheless, applicability of approximation-based modeling for real-world microwave components is hindered by a high nonlinearity of the system characteristics, dimensionality issues, and broad ranges of operating parameters the model should cover to make it practically useful. Performance-driven modeling frameworks deliver a partial mitigation of these problems through appropriate spatial orientation of the metamodel domain, which only encapsulates high-quality designs and not the entire space. Unfortunately, the initial model setup cost is high, as defining the domain requires database designs that need to be a priori acquired. This paper introduces a novel approach, where the database designs are replaced by random observables, and dimensionality of the domain is reduced using spectral analysis thereof. The major contributions of the work include implementation of the explicit dimensionality reduction of the confined surrogate model domain and introducing this concept into a complete cost-efficient framework for modeling of microwave components. Comprehensive benchmarking demonstrates excellent performance of the introduced framework, both in terms of predictive power of the rendered surrogates, their scalability properties, as well as low computational overhead associated with the model setup.