Nonadiabatic transition probabilities for quantum systems in electromagnetic fields: Dephasing and population relaxation due to contact with a bath.

We contrast Dirac's theory of transition probabilities and the theory of nonadiabatic transition probabilities, applied to a perturbed system that is coupled to a bath. In Dirac's analysis, the presence of an excited state |k0⟩ in the time-dependent wave function constitutes a transition. In the nonadiabatic theory, a transition occurs when the wave function develops a term that is not adiabatically connected to the initial state. Landau and Lifshitz separated Dirac's excited-state coefficients into a term that follows the adiabatic theorem of Born and Fock and a nonadiabatic term that represents excitation across an energy gap. If the system remains coherent, the two approaches are equivalent. However, differences between the two approaches arise when coupling to a bath causes dephasing, a situation that was not treated by Dirac. For two-level model systems in static electric fields, we add relaxation terms to the Liouville equation for the time derivative of the density matrix. We contrast the results obtained from the two theories. In the analysis based on Dirac's transition probabilities, the steady state of the system is not an equilibrium state; also, the steady-state population ρkk,s increases with increasing strength of the perturbation and its value depends on the dephasing time T2. In the nonadiabatic theory, the system evolves to the thermal equilibrium with the bath. The difference is not simply due to the choice of basis because the difference remains when the results are transformed to a common basis.

Medicinal plant molecules against hepatitis C virus: Current status and future prospect.

Hepatitis C virus (HCV), a global malady, causes acute and chronic hepatitis leading to permanent liver damage, hepatocellular carcinoma, and death. Modern anti-HCV therapies are efficient, but mostly inaccessible for residents of underdeveloped regions. To innovate more effective treatments at affordable cost, medicinal plant-based products need to be explored. The aim of this article is to review plant constituents in the light of putative anti-HCV mechanisms of action, and discuss existing problems, challenges, and future directions for their potential application in therapeutic settings. One hundred sixty literatures were collected by using appropriate search strings via scientific search engines: Google Scholar, PubMed, ScienceDirect, and Scopus. Bibliography was prepared using Mendeley desktop software. We found a substantial number of plants that were reported to inhibit different stages of HCV life cycle. Traditional medicinal plants such as Phyllanthus amarus Schumach. and Thonn., Eclipta alba (L.) Hassk., and Acacia nilotica (L.) Delile exhibited strong anti-HCV activities. Again, several phytochemicals such as epigallocatechin-3-gallate, honokilol, punicalagin, and quercetin have shown broad-spectrum anti-HCV effect. We have presented promising phytochemicals like silymarin, curcumin, glycyrrhizin, and camptothecin for nanoparticle-based hepatocyte-targeted drug delivery. Nevertheless, only a few animal studies have been performed to validate the anti-HCV effect of these plant products. Again, insufficient clinical evaluation of the safety and effectiveness of herbal medications remain a problem. Selected plants products could be developed as novel therapeutics for HCV patients only after scrupulous evaluation of their safety and efficacy in a clinical set-up.

Quantum transition probabilities due to overlapping electromagnetic pulses: Persistent differences between Dirac's form and nonadiabatic perturbation theory.

The probability of transition to an excited state of a quantum system in a time-dependent electromagnetic field determines the energy uptake from the field. The standard expression for the transition probability has been given by Dirac. Landau and Lifshitz suggested, instead, that the adiabatic effects of a perturbation should be excluded from the transition probability, leaving an expression in terms of the nonadiabatic response. In our previous work, we have found that these two approaches yield different results while a perturbing field is acting on the system. Here, we prove, for the first time, that differences between the two approaches may persist after the perturbing fields have been completely turned off. We have designed a pair of overlapping pulses in order to establish the possibility of lasting differences, in a case with dephasing. Our work goes beyond the analysis presented by Landau and Lifshitz, since they considered only linear response and required that a constant perturbation must remain as t → ∞. First, a "plateau" pulse populates an excited rotational state and produces coherences between the ground and excited states. Then, an infrared pulse acts while the electric field of the first pulse is constant, but after dephasing has occurred. The nonadiabatic perturbation theory permits dephasing, but dephasing of the perturbed part of the wave function cannot occur within Dirac's method. When the frequencies in both pulses are on resonance, the lasting differences in the calculated transition probabilities may exceed 35%. The predicted differences are larger for off-resonant perturbations.

Variance of the energy of a quantum system in a time-dependent perturbation: Determination by nonadiabatic transition probabilities.

For a quantum system in a time-dependent perturbation, we prove that the variance in the energy depends entirely on the nonadiabatic transition probability amplitudes bk(t). Landau and Lifshitz introduced the nonadiabatic coefficients for the excited states of a perturbed quantum system by integrating by parts in Dirac's expressions for the coefficients ck (1)(t) of the excited states to first order in the perturbation. This separates ck (1)(t) for each state into an adiabatic term ak (1)(t) and a nonadiabatic term bk (1)(t). The adiabatic term follows the adiabatic theorem of Born and Fock; it reflects the adjustment of the initial state to the perturbation without transitions. If the response to a time-dependent perturbation is entirely adiabatic, the variance in the energy is zero. The nonadiabatic term bk (1)(t) represents actual excitations away from the initial state. As a key result of the current work, we derive the variance in the energy of the quantum system and all of the higher moments of the energy distribution using the values of |bk(t)|2 for each of the excited states along with the energy differences between the excited states and the ground state. We prove that the same variance (through second order) is obtained in terms of Dirac's excited-state coefficients ck(t). We show that the results from a standard statistical analysis of the variance are consistent with the quantum results if the probability of excitation Pk is set equal to |bk(t)|2, but not if the probability of excitation is set equal to |ck(t)|2. We illustrate the differences between the variances calculated with the two different forms of Pk for vibration-rotation transitions of HCl in the gas phase.

Expression of Duplex shRNAs through a Lentiviral Vector against Cellular and Viral Genes Inflicts Sustained Inhibition of Hepatitis C Virus Replication.

BACKGROUND: The RNAi-based transient therapeutic approach has been well explored for its potential against the hepatitis V virus (HCV). However, to achieve a sustained virological response, a consistent presence of siRNA is needed and it can be achieved by constitutively expressing shRNAs. In this context, the lentiviral vector has emerged as an attractive tool for shRNA delivery against HCV. METHODS: We monitored HCV inhibition after single and multiple rounds of siRNA treatments against La autoantigen and HCV-NS5B in Huh-7.5 cells infected with the FL-J6/JFH chimeric HCV strain. A bicistronic self-inactivating third-generation lentiviral vector expressing shRNA under U6 and H1 promoters was constructed. To ascertain the long-term HCV inhibition, cells were transduced with lentiviral vectors and HCV inhibition was monitored by RT-PCR and Western blotting at regular intervals. RESULTS: We observed transient antiviral activity after a single round of siRNA treatment, and consecutive rounds of treatments with siRNA demonstrated a sustained HCV inhibition. Delivery of duplex shRNA expressing lentiviral vectors provided constant expression of shRNA leading to synergistic and sustained HCV inhibition. CONCLUSION: A lentiviral vector-based delivery system is a "single-shot" therapeutic strategy. It can express duplex shRNA for long-term synergistic inhibition of HCV and qualify as a promising therapeutic approach for sustained inhibition of HCV replication.

Quantum transition probabilities during a perturbing pulse: Differences between the nonadiabatic results and Fermi's golden rule forms.

For a perturbed quantum system initially in the ground state, the coefficient ck(t) of excited state k in the time-dependent wave function separates into adiabatic and nonadiabatic terms. The adiabatic term ak(t) accounts for the adjustment of the original ground state to form the new ground state of the instantaneous Hamiltonian H(t), by incorporating excited states of the unperturbed Hamiltonian H0 without transitions; ak(t) follows the adiabatic theorem of Born and Fock. The nonadiabatic term bk(t) describes excitation into another quantum state k; bk(t) is obtained as an integral containing the time derivative of the perturbation. The true transition probability is given by bk(t) 2, as first stated by Landau and Lifshitz. In this work, we contrast bk(t) 2 and ck(t) 2. The latter is the norm-square of the entire excited-state coefficient which is used for the transition probability within Fermi's golden rule. Calculations are performed for a perturbing pulse consisting of a cosine or sine wave in a Gaussian envelope. When the transition frequency ωk0 is on resonance with the frequency ω of the cosine wave, bk(t) 2 and ck(t) 2 rise almost monotonically to the same final value; the two are intertwined, but they are out of phase with each other. Off resonance (when ωk0 ≠ ω), bk(t) 2 and ck(t) 2 differ significantly during the pulse. They oscillate out of phase and reach different maxima but then fall off to equal final values after the pulse has ended, when ak(t) ≡ 0. If ωk0 < ω, bk(t) 2 generally exceeds ck(t) 2, while the opposite is true when ωk0 > ω. While the transition probability is rising, the midpoints between successive maxima and minima fit Gaussian functions of the form a exp[-b(t - d)2]. To our knowledge, this is the first analysis of nonadiabatic transition probabilities during a perturbing pulse.

Nonadiabatic transition probabilities in a time-dependent Gaussian pulse or plateau pulse: Toward experimental tests of the differences from Dirac's transition probabilities.

For a quantum system subject to a time-dependent perturbing field, Dirac's analysis gives the probability of transition to an excited state |k⟩ in terms of the norm square of the entire excited-state coefficient ck(t) in the wave function. By integrating by parts in Dirac's equation for ck(t) at first order, Landau and Lifshitz separated ck (1)(t) into an adiabatic term ak (1)(t) that characterizes the gradual adjustment of the ground state to the perturbation without transitions and a nonadiabatic term bk (1)(t) that depends explicitly on the time derivative of the perturbation at times t' ≤ t. Landau and Lifshitz stated that the probability of transition in a pulsed perturbation is given by |bk(t)|2, rather than by |ck(t)|2. We use the term "transition probability" to refer to the probability that a true excited-state component is present in the time-evolved wave function, as opposed to a smooth modification of the initial state. In recent work, we have examined the differences between |bk(t)|2 and |ck(t)|2 when a system is perturbed by a harmonic wave in a Gaussian envelope. We showed that significant differences exist when the frequency of the harmonic wave is off-resonance with the transition frequency. In this paper, we consider Gaussian perturbations and pulses that rise via a half Gaussian shoulder to a level plateau and later return to zero via a down-going half Gaussian. While the perturbation is constant, the transition probability |bk(t)|2 does not change. By contrast, |ck(t)|2 continues to oscillate while the perturbation is constant, and its time averaged value differs from |bk(t)|2. We suggest a general type of experiment to prove that the transition probability is given by |bk(t)|2, not |ck(t)|2. We propose a ratio test that does not require accurate knowledge of transition matrix elements or absolute field intensities.

Depolarization of mitochondrial membrane potential is the initial event in non-nucleoside reverse transcriptase inhibitor efavirenz induced cytotoxicity.

Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) and an active constituent of the highly active antiretroviral therapy regime. It has significantly contributed in control and management of human immunodeficiency virus propagation. However, EFV administration has also led to severe adverse effects, several reports highlighted the role of EFV in mitochondrial dysfunction and toxicity but the molecular mechanism has been poorly understood. In present study, human hepatoma cells Huh 7.5 were treated with clinically relevant concentrations of EFV and parameters like cytotoxicity, mitochondrial transmembrane potential, mitochondrial morphology, cytochrome c release, mitochondria-mediated apoptosis, mtDNA and mtRNA levels and EFV distribution into mitochondrial compartment were evaluated to understand sequence of events leading to cell death in EFV-treated cells. EFV at its clinically relevant concentration was significantly toxic after 48 and 72 h of treatments. EFV-mediated toxicity is initiated with the permeabilization of mitochondrial outer membrane and change in mitochondrial membrane potential (Δψm) which triggers a series of events like cytochrome c release, alteration in mitochondrial morphology and mitochondria-mediated apoptosis. Total mitochondrial content is reduced after 48 h of EFV treatment at IC50 concentration which is also reflected in reduced mitochondrial DNA and RNA levels. After detecting EFV in mitochondrial compartment after 12 h of incubation with EFV, we hypothesize that EFV being a lipophilic molecule is internalized into the mitochondrial compartment causing depolarization of Δψm which subsequently leads to a cascade of events causing cell death.

Anti-HCV Activity from Semi-purified Methanolic Root Extracts of Valeriana wallichii.

Hepatitis C virus (HCV) is a serious global health problem affecting approximately 130-150 million individuals. Presently available direct-acting anti-HCV drugs have higher barriers to resistance and also improved success rate; however, cost concerns limit their utilization, especially in developing countries like India. Therefore, development of additional agents to combat HCV infection is needed. In the present study, we have evaluated anti-HCV potential of water, chloroform, and methanol extracts from roots of Valeriana wallichii, a traditional Indian medicinal plant. Huh-7.5 cells infected with J6/JFH chimeric HCV strain were treated with water, chloroform, and methanol extracts at different concentrations. Semi-quantitative reverse transcription polymerase chain reaction result demonstrated that methanolic extract showed reduction in HCV replication. The methanolic extract was fractionated by thin layer chromatography, and the purified fractions (F1, F2, F3, and F4) were checked for anti-HCV activity. Significant viral inhibition was noted only in F4 fraction. Further, intrinsic fluorescence assay of purified HCV RNA-dependent RNA polymerase NS5B in the presence of F4 resulted in sharp quenching of intrinsic fluorescence with increasing amount of plant extract. Our results indicated that methanolic extract of V. wallichii and its fraction (F4) inhibited HCV by binding with HCV NS5B protein. The findings would be further investigated to identify the active principle/lead molecule towards development of complementary and alternative therapeutics against HCV. Copyright © 2017 John Wiley & Sons, Ltd.

Infantile Tremor Syndrome and Subdural Hemorrhage in an Infant with Cystic Fibrosis.

Cystic fibrosis (CF), an autosomal recessive disease with multi-system involvement, may present with bleeding in infancy owing to vitamin K malabsorption. Infantile tremor syndrome (ITS) is an obscure condition associated with vitamin B12 and other micronutrient deficiencies, described predominantly in Indian subcontinent. We describe an infant presenting with ITS and chronic subdural hemorrhage. He was subsequently diagnosed to have CF. The ITS and subdural hemorrhage is rarely reported in children with CF. In the background of increasing recognition of CF in Indian children, this case demonstrates a new association of this disease.