Predicting multiple observations in complex systems through low-dimensional embeddings.

Forecasting all components in complex systems is an open and challenging task, possibly due to high dimensionality and undesirable predictors. We bridge this gap by proposing a data-driven and model-free framework, namely, feature-and-reconstructed manifold mapping (FRMM), which is a combination of feature embedding and delay embedding. For a high-dimensional dynamical system, FRMM finds its topologically equivalent manifolds with low dimensions from feature embedding and delay embedding and then sets the low-dimensional feature manifold as a generalized predictor to achieve predictions of all components. The substantial potential of FRMM is shown for both representative models and real-world data involving Indian monsoon, electroencephalogram (EEG) signals, foreign exchange market, and traffic speed in Los Angeles Country. FRMM overcomes the curse of dimensionality and finds a generalized predictor, and thus has potential for applications in many other real-world systems.

Comparative Evaluation of Surgical Operability with and without Induction Chemotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma.

To compare and evaluation of surgical operability with and without induction chemotherapy in locally advanced head and neck squamous cell carcinoma. Head and neck malignancy grossly refers to squamous cell carcinomas of head and neck (HNSCC) have multiple treatment modalities and strategies, when opted in an appropriate manner renders tumours curable. The aim of this study is to compare and evaluation of surgical operability with and without induction chemotherapy in locally advanced head and neck squamous cell carcinoma. A prospective observational study involving 50 patients of histologically proven squamous cell carcinoma of head and neck region. Patients were categorized into two major groups, group-1 patients included resectable tumour stage and group-2 included unresectable tumour stage. Both groups were compared after appropriate chemotherapy and surgical intervention. There were a total of 78% males and 22% females with majority of patients in age group of 41-60 years. 54% patients had ulcerative type of growth pattern and most patients had primary site of lesion in oral cavity. 50% patients had moderately differentiated squamous cell carcinoma. Induction chemotherapy was considered in 70% of patients, while majority of patients were belonging to T4N2M0 stage. In this study, we recommend that the borderline category of patients who are initially in an unresectable tumour stage can undergo induction chemotherapy to downstage and shrink the tumour to a resectable stage following which the appropriate surgical intervention should be done with a close monitoring and sustained follow up to prevent recurrence.

Spin qubits of Cu(II) doped in Zn(II) metal-organic frameworks above microsecond phase memory time.

With the aim of creating Cu(II) spin qubits in a rigid metal-organic framework (MOF), this work demonstrates a doping of 5 %, 2 %, 1 %, and 0.1 % mol of Cu(II) ions into a perovskite-type MOF [CH6 N3 ][ZnII (HCOO)3 ]. The presence of dopant Cu(II) sites are confirmed with anisotropic g-factors (gx =2.07, gy =2.12, and gz =2.44) in the S=1/2 system by experimentally and theoretically. Magnetic dynamics indicate the occurrence of a slow magnetic relaxation via the direct and Raman processes under an applied field, with a relaxation time (τ) of 3.5 ms (5 % Cu), 9.2 ms (2 % Cu), and 15 ms (1 % Cu) at 1.8 K. Furthermore, pulse-ESR spectroscopy reveals spin qubit properties with a spin-spin relaxation (phase memory) time (T2 ) of 0.21 µs (2 %Cu), 0.39 µs (1 %Cu), and 3.0 µs (0.1 %Cu) at 10 K as well as Rabi oscillation between MS =±1/2 spin sublevels. T2 above microsecond is achieved for the first time in the Cu(II)-doped MOFs. It can be observed at submicrosecond around 50 K. These spin relaxations are very sensitive to the magnetic dipole interactions relating with cross-relaxation between the Cu(II) sites and can be tuned by adjusting the dopant concentration.

Expression of mammalian cell entry genes in clinical isolates of M. tuberculosis and the cell entry potential and immunological reactivity of the Rv0590A protein.

Mammalian cell entry (mce) operons play a vital role in cell invasion and survival of M. tuberculosis. Of the mce genes, the function of Rv0590A is still unknown. The present study was performed to investigate the function and immunogenic properties of the protein Rv0590A. Human leukemia monocytic cell line (THP-1) derived macrophages were infected with M. tuberculosis H37Rv at 3, 6, and 24 h of infection. The maximum colony forming units (CFU) were observed at 6 h (p < 0.005), followed by 3 h after infection. M. tuberculosis H37Rv and clinical isolates representative of Delhi/CAS, EAI, Beijing, Haarlem and Euro-American-superlineage were included in the study for expression analysis of mce1A, mce2A, mce3A, mce4A, and Rv0590A genes. Maximum upregulation of all mce genes was observed at 3 h of infection. All the five clinical isolates and H37Rv upregulated Rv0590A at various time points. Macrophage infection with M. tuberculosis H37Rv-overexpressing Rv0590A gene showed higher intracellular CFU as compared to that of wild-type H37Rv. Further, purified Rv0590A protein stimulated the production of TNFα, IFNγ, and IL-10 in macrophages. Thus, Rv0590A was found to be involved in cell invasion and showed good immunological response.

Development of substituted benzylidene derivatives as novel dual cholinesterase inhibitors for Alzheimer's treatment.

Leading pathological markers of Alzheimer's disease (AD) include Acetylcholinesterase (AChE), Butyrylcholinesterase (BuChE), Amyloid beta (Aß) and reactive oxygen species (ROS). Indole derivatives were identified and optimized to improve the potency against AChE, BuChE, Aß and ROS. The lead molecule IND-30 was found to be selective for AChE (selectivity ratio: 22.92) in comparison to BuChE and showed maximum inhibition potential for human AChE (IC50: 4.16 ± 0.063 µM). IND-30 was found to be safe on the SH-SY5Y cell line until the dose of 30 mM. Further, molecule IND-30 was evaluated for its ability to inhibit AChE-induced Aß aggregation at 0.5, 10 and 20 µM doses. Approximately, 50% of AChE-induced Aß aggregation was inhibited by IND-30. Thus, IND-30 was found to be multitargeting for AD.

Slow magnetic relaxation in a ferromagnetic CuII chain complex, induced by a phonon bottleneck effect.

The first slow magnetic relaxation in a ferromagnetic Cu(II) chain compound, Cu(dipic)(OH2)2 (dipicH2 = pyridine-2,6-dicarboxylic acid), induced by a phonon bottleneck effect under a magnetic field of 0.6 T, with a relaxation time of 2.2 s at 2.8 K, was observed.

Spin dynamics in a Heisenberg weak antiferromagnetic chain of an iodide-bridged Cu(II) complex.

[CuII(chxn)2I]I (chxn = 1R,2R-diaminocyclohexane) has been synthesized, which is the first report of an iodide-bridged Cu(II) chain structure. This chain compound shows S = 1/2 Heisenberg weak antiferromagnetism (J = -0.3 cm-1) and magnetic relaxation (τ = 43 ms at 1.8 K) with a Raman process in a static field.

Creation of a Field-Induced Co(II) Single-Ion Magnet by Doping into a Zn(II) Diamagnetic Metal-Organic Framework.

The combination of single-ion magnets (SIMs) and metal-organic frameworks (MOFs) is expected to produce new quantum materials. The principal issue to be solved in this regard is the development of new strategies for the synthesis of SIM-MOFs. This work demonstrates a new simple strategy for the synthesis of SIM-MOFs where a diamagnetic MOF is used as the framework into which the SIM sites are doped. 1, 0.5, and 0.2 mol% of the Co(II) ions are doped into the Zn(II) sites of [CH6 N3 ][ZnII (HCOO)3 ]. The doped Co(II) sites in the MOFs perform as SIM with a positive D term of zero-field splitting. The longest magnetic relaxation time is 150 ms (0.2 mol% Co) at 1.8 K under a static field of 0.1 T. Temperature dependency of the relaxation time suggests suppressing magnetic relaxation by reduction of spin-spin interaction upon doping in the rigid framework. Thus, this work represents a proof of concept for the creation of a single-ion doped magnet in the MOF. This simple synthetic strategy will be widely applied for the creation of quantum magnetic materials.

Quinoid-Based Three-Dimensional Metal-Organic Framework Fe2(dhbq)3: Porosity, Electrical Conductivity, and Solid-State Redox Properties.

We report the synthesis, characterization, and electronic properties of the quinoid-based three-dimensional metal-organic framework [Fe2(dhbq)3]. The MOF was synthesized without using cations as a template, unlike other reported X2dhbq3-based coordination polymers, and the crystal structure was determined by using single-crystal X-ray diffraction. The crystal structure was entirely different from the other reported [Fe2(X2dhbq3)]2-; three independent 3D polymers were interpenetrated to give the overall structure. The absence of cations led to a microporous structure, investigated by N2 adsorption isotherms. Temperature dependence of electrical conductivity data revealed that it exhibited a relatively high electrical conductivity of 1.2 × 10-2 S cm-1 (Ea = 212 meV) due to extended d-π conjugation in a three-dimensional network. Thermoelectromotive force measurement revealed that it is an n-type semiconductor with electrons as the majority of charge carriers. Structural characterization and spectroscopic analyses, including SXRD, Mössbauer, UV-vis-NIR, IR, and XANES measurements, evidenced the occurrence of no mixed valency based on the metal and the ligand. [Fe2(dhbq)3] upon incorporating as a cathode material for lithium-ion batteries engendered an initial discharge capacity of 322 mAh/g.

Study of interaction and complete merging of binary cyclones using complex networks.

Cyclones are among the most hazardous extreme weather events on Earth. In certain scenarios, two co-rotating cyclones in close proximity to one another can drift closer and completely merge into a single cyclonic system. Identifying the dynamic transitions during such an interaction period of binary cyclones and predicting the complete merger (CM) event are challenging for weather forecasters. In this work, we suggest an innovative approach to understand the evolving vortical interactions between the cyclones during two such CM events (Noru-Kulap and Seroja-Odette) using time-evolving induced velocity-based unweighted directed networks. We find that network-based indicators, namely, in-degree and out-degree, quantify the changes in the interaction between the two cyclones and are excellent candidates to classify the interaction stages before a CM. The network indicators also help to identify the dominant cyclone during the period of interaction and quantify the variation of the strength of the dominating and merged cyclones. Finally, we show that the network measures also provide an early indication of the CM event well before its occurrence.

Smart Advancements for Targeting Solid Tumors via Protein and Peptide Drug Delivery (PPD).

Proteins and peptides possess considerable potential in treating solid tumors because of their unique properties. At present, there are over 100 peptide-based formulations on the market. Today, peptides and proteins are in more demand due to their selective nature and high target-binding efficiency. Targeting solid tumors with compounds of molecular weight less than 10 kDa are much more desirable because they undergo excessive penetration in view of the fact that they are small sized. The solid tumors have thick tissues and possess excessive interstitial fluid pressure, because of which high molecular compounds cannot enter. The properties of proteins and peptides induce low toxic effects and lessen the major side effects caused by chemical-based drugs. However, their delivery is quite challenging as most proteins and peptides stop functioning therapeutically when following a parenteral route of administration. This paper elaborates on the importance of new age formulations of peptides and proteins followed by their recently documented advancements that increase their stability and delay their metabolism, which helps to target solid tumors.

Quantum dots in the biomedical world: A smart advanced nanocarrier for multiple venues application.

Quantum dots (QDs) are semiconducting nanoparticles having different optical and electrical properties when compared to larger particles. They exhibit photoluminescence when irradiated with ultraviolet light, which is due to the transition of an excited electron from the valence band to the conductance band followed by the return of the exciting electron back into the valence band. The size and material of QDs can affect their optical and other properties too. The QDs possess special attributes like high brightness, protection from photobleaching, photostability, color tunability, low toxicity, low production cost, a multiplexing limit, and a high surface-to-volume proportion, which make them a promising tool for biomedical applications. Here, in this study, we summarize the utilization of QDs in different applications including bioimaging, diagnostics, immunostaining, single-cell analysis, drug delivery, and protein detection. Moreover, we discuss the advantages and challenges of using QDs in biomedical applications when compared with other conventional tools.

Comparative assessment of cephalometric with its analogous photographic variables.

Objective: The purpose of this study was to evaluate the accuracy of photographic measurements and compare it with its analogous cephalometric variables. Materials and Methods: Lateral cephalograms and standardized facial profile photographs were obtained from a sample of 120 subjects (92 females, 28 males; age 12-22 years with mean age of 17.5 years). A total of 4 linear and 7 angular measurements along with 3 ratios analogous to one another were measured on both. Descriptive statistics for all measurements were computed. Pearson's correlation coefficients were computed between analogous measurements, and regression analysis was done for each variable measured on the photograph to accurately predict the cephalometric variable. Results: The reliability of the standardized photographic technique was satisfactory. Most photographic measurements showed highly significant correlations (P < 0.001) with cephalometric variables. Among all measurements used, the A'N'B' angle was the most effective in explaining the variability of its analogous cephalometric (r2= 0.35). The Frankfort-mandibular plane angle' angle showed best results for vertical assessment (r2= 0.81) along with anterior face height (AFH) and lower anterior facial height (r2= 0.859) and ratio lower posterior facial height/AFH (r2= 0.702). Conclusions: Although we cannot rule out lateral cephalogram as the primary record in orthodontics, photographic assessment can always be used through proper standardization, as an alternative diagnostic aid, and also for large-scale epidemiological purposes and places with unavailability of cephalostat.

Perspectives on the importance of complex systems in understanding our climate and climate change-The Nobel Prize in Physics 2021.

The Nobel Prize in Physics 2021 was awarded to Syukuro Manabe, Klaus Hasselmann, and Giorgio Parisi for their "groundbreaking contributions to our understanding of complex systems," including major advances in the understanding of our climate and climate change. In this Perspective article, we review their key contributions and discuss their relevance in relation to the present understanding of our climate. We conclude by outlining some promising research directions and open questions in climate science.

Bromine Vapor Induced Continuous p- to n-Type Conversion of a Semiconductive Metal-Organic Framework Cu[Cu(pdt)2].

Guest-promoted modulation of the electronic states in metal-organic frameworks (MOFs) has brought about a new field of interdisciplinary research, including host-guest chemistry and solid-state physics. Although there are dozens of studies on guest-promoted enhancement of the electrical conductivity properties, including stoichiometry, conductive carriers and structure-property relationships have been scarcely studied in detail. Herein, we studied the effects of continuous and controlled bromine vapor doping on structural, optical, thermoelectric, and semiconducting properties of Cu[Cu(pdt)2] (pdt = 2,3-pyrazinedithiolate) as a function of bromine stoichiometry. We demonstrated that the same material could act as both p- and n-type semiconductors by tuning the stoichiometry of Br doped in Brx@Cu[Cu(pdt)2], and a change in the charge-carrier type from holes in pristine MOF to electrons upon bromine vapor doping was observed. Bromine molecules acted as an oxidant, causing the selective oxidation of [CuII(pdt)2] in the host framework. In addition, a redox hopping pathway between the partially oxidized CuII/CuIII center contributed to the enhancement of the electrical conductivity of the MOF.

Whole genome sequencing of isoniazid monoresistant clinical isolates of Mycobacterium tuberculosis reveals novel genetic polymorphisms.

In an attempt to uncover genotypic indicators for isoniazid (INH) resistance in M. tuberculosis, in addition to the canonical mutations in genes associated with INH resistance, including katG, inhA and fabG promoter; we analyzed, two INH monoresistant isolates, ASTS24/13 (INHR1) and SHR1/14 (INHR2). Targeted Sanger sequencing detected a canonical mutation at katG315 only in INHR2. Infection of THP-1 cells and exposure to antituberculosis drugs led to two-fold increase in the minimum inhibitory concentration of INH in INHR2. Whole genome sequences revealed that INHR1 and INHR2 belonged to Delhi Central Asian Strain and East African Indian lineages, respectively. The sequences were compared with INH susceptible isolates with the same lineage as the INH monoresistant strains. INHR1 had a novel unique mutation STOP420Trp in the efflux pump gene Rv0849, while INHR2 had a novel mutation Arg579Ser in efflux pump gene mmpL5. Comparison of lipid associated genes showed novel mutations in INHR1 in fadE16, fadD3 and fbpD; while INHR2 had mutations in fadE1, Rv0145, Rv1425, fadD9 and mmaA3. Both isolates also demonstrated novel mutations in cell wall associated genes. Our study highlights the importance of searching for alternate mechanisms of INH resistance that may contribute to the development of more comprehensive diagnostic tools.

Indene-Derived Hydrazides Targeting Acetylcholinesterase Enzyme in Alzheimer's: Design, Synthesis, and Biological Evaluation.

As acetylcholinesterase (AChE) plays a crucial role in advancing Alzheimer's disease (AD), its inhibition is a promising approach for treating AD. Sulindac is an NSAID of the aryl alkanoic acid class, consisting of a indene moiety, which showed neuroprotective behavior in recent studies. In this study, newer Indene analogs were synthesized and evaluated for their in vitro AChE inhibition. Additionally, compared with donepezil as the standard drug, these Indene analogs were accessed for their cell line-based toxicity study on SH-SY5Y cell line. The molecule SD-30, having hydrogen bond donor (HBD) at para-position, showed maximum AChE inhibition potential (IC50 13.86 ± 0.163 µM) in the indene series. Further, the SD-30 showed maximum BuChE inhibition potential (IC50 = 48.55 ± 0.136 µM) with a selectivity ratio of 3.50 and reasonable antioxidant properties compared to ascorbic acid (using DPPH assay). SD-30 (at a dose level: of 10 µM, 20 µM) effectively inhibited AChE-induced Aß aggregation and showed no significant toxicity up to 30 mM against SH-SY5Y cell lines.

Preclinical Models for Alzheimer's Disease: Past, Present, and Future Approaches.

A robust preclinical disease model is a primary requirement to understand the underlying mechanisms, signaling pathways, and drug screening for human diseases. Although various preclinical models are available for several diseases, clinical models for Alzheimer's disease (AD) remain underdeveloped and inaccurate. The pathophysiology of AD mainly includes the presence of amyloid plaques and neurofibrillary tangles (NFT). Furthermore, neuroinflammation and free radical generation also contribute to AD. Currently, there is a wide gap in scientific approaches to preventing AD progression. Most of the available drugs are limited to symptomatic relief and improve deteriorating cognitive functions. To mimic the pathogenesis of human AD, animal models like 3XTg-AD and 5XFAD are the primarily used mice models in AD therapeutics. Animal models for AD include intracerebroventricular-streptozotocin (ICV-STZ), amyloid beta-induced, colchicine-induced, etc., focusing on parameters such as cognitive decline and dementia. Unfortunately, the translational rate of the potential drug candidates in clinical trials is poor due to limitations in imitating human AD pathology in animal models. Therefore, the available preclinical models possess a gap in AD modeling. This paper presents an outline that critically assesses the applicability and limitations of the current approaches in disease modeling for AD. Also, we attempted to provide key suggestions for the best-fit model to evaluate potential therapies, which might improve therapy translation from preclinical studies to patients with AD.

An overview of pulmonary infections due to rapidly growing mycobacteria in South Asia and impressions from a subtropical region.

Background: Rapidly growing mycobacteria (RGM) comprise nearly half of the validated species of nontuberculous mycobacteria (NTM) and have been reported to have a higher incidence in Asia as compared to Europe and America. There is limited information on RGM infections from South Asia. Hence, the present study aimed to ascertain the incidence of pulmonary infections due to RGM in Delhi and to review the status of available information on the prevalence of RGM in South Asia, a region endemic for tuberculosis. Methods: We analyzed 933 mycobacterial isolates obtained from pulmonary samples in Delhi and performed species identification by polymerase chain reaction (PCR)-restriction analysis (restriction fragment length polymorphism) and line probe assay. Drug susceptibility testing (DST) was performed by broth microdilution method. We also reviewed reports available on pulmonary infections in South Asia, attributed to RGM. Results: Of the 933 mycobacterial isolates studied, NTM were identified in 152 (16.3%). Of these, 65/152 (42.8%) were RGM comprising Mycobacterium fortuitum (34/65; 52.3%), Mycobacterium abscessus (25/65; 38.5%), Mycobacterium chelonae (3/65; 4.61%), Mycobacterium mucogenicum (2/65; 3.1%), and Mycobacterium smegmatis (1/65; 1.5%). On applying the American Thoracic Society/Infectious Diseases Society of America guidelines, 11/25 (44%) M. abscessus, 3/3 (100%) M. chelonae, and both isolates of M. mucogenicum were found to be clinically relevant. DST revealed that maximum susceptibility of the RGM was seen to linezolid, clarithromycin, and amikacin. Conclusions: Of the RGM isolated in the present study, 16/65 (24.6%) were found to be clinically relevant. Hence, it is important to recognize these organisms as potential pathogens to identify patients with RGM disease to initiate appropriate therapy.