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Introduction: Fluoride agents to prevent white spot lesions are used often during orthodontic treatment. The beneficial effects of fluoride, when consumed within permissible limits on dental structures, are well known. Their implications on underlying biological tissues, however, are unknown. Mouthwashes and dentifrices with fluorides are associated with metal ion release into the mouth with possible cell genotoxicity. Since these cariostatic agents are frequently used during orthodontic therapy, a deeper understanding of the effects of fluoride on oral tissues was considered necessary. Methodology: Three groups of patients (30 each)—group 1 (untreated controls), group 2 (non-fluoridated), and group 3 (Fluoridated) were analyzed. Patients in groups 2 and 3 were bonded with the same bracket prescription and treated with similar archwire sequences. Buccal mucosal cells at 4 specific time periods (before treatment, 1 week, 30 days, and 6 months) were collected, using a wooden tongue depressor, and assessed for any nuclear abnormalities. Comparisons of changes were made with an untreated control group and also between the non-fluoridated and fluoridated groups. Relevant conclusions were drawn after analysis of the results. Results: Greater number of nuclei were observed at the 30-day time interval in the fluoridated group, which was statistically significant at P < .001. Conclusion: Use of fluoridated oral hygiene products in patients undergoing fixed orthodontic treatment with NiTi archwires could increase the risk of micronuclei formation in buccal mucosal cells.

Rectovaginal group B streptococcal (GBS) colonisation affects approximately 30% of pregnant women, which significantly increases the use of antibiotics in mothers and babies. In this review, we aim to answer two questions: (i) In pregnant women, does the use of probiotics prevent GBS colonisation prior to delivery when compared with placebo; and (ii) In GBS positive pregnant women, does the use of probiotics reduce the risk of GBS colonisation prior to delivery when compared with standard treatment. Pubmed, Cochrane library, EMBASE, OVID, clinical trials.gov, grey literature and conference proceedings were systematically searched to identify eligible trials. References of included trials were also reviewed. A total of four studies (n = 402) were included in the final review. Two studies reported on the prevention of GBS colonisation in healthy pregnant women, and two studies reported on the rate of GBS clearance after probiotic administration. Meta-analysis of the two studies using random effects model indicated that GBS clearance with probiotics was not statistically significant with odds ratio 2.12 (95% confidence interval 0.60-7.50, P = 0.17). Collection of adverse events data was not a primary or secondary aim in any of the studies. We conclude that there is limited evidence to recommend the regular use of probiotics to minimise the risk of GBS colonisation. Results from ongoing studies are likely to add to the current existing evidence.

Respiratory diseases are an important cause of morbidity and mortality worldwide. Although conventional histopathology is the gold standard for their diagnosis, cytology is a useful adjunctive diagnostic test. In the present study we evaluated the efficacy of cytology in providing a rapid diagnosis. We included lesions which were both visible and not visible on bronchoscopy. We evaluated the role of bronchoalveolar lavage (BAL), brush cytology and imprint smears both separately and in combination, and compared them with the histopathological findings of transbronchial lung biopsy (TBLB). Among 100 cases the highest concordance was seen between imprint cytology (77.78%) and biopsy for malignancy, followed by bronchoalveolar lavage (40.91%) and brush cytology (40.00%). The concordance and level of agreement between cytology and biopsy was very poor in general for non-neoplastic lesions. However, it increased when BAL and imprint smears (42.50%) were performed together, compared to other combinations. We recommend a combination of cytological techniques in suspected cases of malignancy, as more useful than a single test, and to include imprint smears in all cases. However, biopsy remains the gold standard for diagnosis in non-neoplastic lung disease.

This paper reports on the development of a novel CMOS device employing lead-sensing bacteria to assay lead in drinking water. The objective of the PlomBOX project is to develop a low-cost sensor (£10) which can expedite access to on-demand assay methods and thus help mitigate lead intake through contaminated drinking water. The project follows three development paths: a) Certain bacteria can fluoresce or change colour when in the presence of lead. A genetically modified strain of Escherichia coli sensitive to lead concentrations up to 10 ppb is being developed. This constitutes the biosensor that fluoresces in proportion to the presence of lead. b) Bacteria response is imaged using a microprocessor (ESP32) with a camera module. This constitutes the optical metrology component of the PlomBOX. c) Data acquisition and control of the PlomBOX is achieved through a Bluetooth connection with the PlomApp, a custom-developed mobile phone application. Data are sent from the PlomApp to a database where a bespoke automated analysis software provides a result of the lead concentration in a sample of water. This paper reports on the instrumentation challenges of developing the electronics for the PlomBOX and on the first prototype.

Axion Dark Matter eXperiment (ADMX) ultra low noise haloscope technology has enabled the successful completion of two science runs (1A and 1B) that looked for dark matter axions in the $2.66$ to $3.1$ $\mu$eV mass range with Dine-Fischler-Srednicki-Zhitnisky (DFSZ) sensitivity Ref. [1,2]. Therefore, it is the most sensitive axion search experiment to date in this mass range. We discuss the technological advances made in the last several years to achieve this sensitivity, which includes the implementation of components, such as state-of-the-art quantum limited amplifiers and a dilution refrigerator. Furthermore, we demonstrate the use of a frequency tunable Microstrip Superconducting Quantum Interference Device (SQUID) Amplifier (MSA), in Run 1A, and a Josephson Parametric Amplifier (JPA), in Run 1B, along with novel analysis tools that characterize the system noise temperature., Comment: 23 pages, 28 figures

We describe the first implementation of a Josephson Traveling Wave Parametric Amplifier (JTWPA) in an axion dark matter search. The operation of the JTWPA for a period of about two weeks achieved sensitivity to axion-like particle dark matter with axion–photon couplings above 10−13 Ge V−1 over a narrow range of axion masses centered around 19.84 µeV by tuning the resonant frequency of the cavity over the frequency range of 4796.7–4799.5 MHz. The JTWPA was operated in the insert of the axion dark matter experiment as part of an independent receiver chain that was attached to a 0.56-l cavity. The ability of the JTWPA to deliver high gain over a wide (3 GHz) bandwidth has engendered interest from those aiming to perform broadband axion searches, a longstanding goal in this field.

This paper reports on a cavity haloscope search for dark matter axions in the galactic halo in the mass range $2.81$-$3.31$ ${\mu}eV$. This search excludes the full range of axion-photon coupling values predicted in benchmark models of the invisible axion that solve the strong CP problem of quantum chromodynamics, and marks the first time a haloscope search has been able to search for axions at mode crossings using an alternate cavity configuration. Unprecedented sensitivity in this higher mass range is achieved by deploying an ultra low-noise Josephson parametric amplifier as the first stage signal amplifier.

An axion is a particle that could resolve some issues with strong interaction CP symmetry and dark matter. A tunable microwave cavity permeated by a strong external magnetic field can be used to detect axions. The Axion Dark Matter eXperiment (ADMX) has developed a four-cavity array design to explore the axion mass range of 5–9 μeV. Tuning of each cavity frequency is done primarily by a coarse tuning rod, with a fine tuning rod used to lock frequencies together. Aluminum prototypes at 1:3 scale have been built and tested. At 300 K, the TM010 frequency varied from 4.4 to 6.4 GHz and crossed three TE modes. Electroplating pure aluminum on the cavity improved the Q factor by 27%. Preliminary results from 4.2 K test showed a 2% reduction of resonant frequency and an improvement in Q by a factor of 2.7 compared to the 300 K values.

Searching for axion dark matter, the ADMX collaboration acquired data from January to October 2018, over the mass range 2.81--3.31 $\mu$eV, corresponding to the frequency range 680--790 MHz. Using an axion haloscope consisting of a microwave cavity in a strong magnetic field, the ADMX experiment excluded Dine-Fischler-Srednicki-Zhitnisky (DFSZ) axions at 100% dark matter density over this entire frequency range, except for a few gaps due to mode crossings. This paper explains the full ADMX analysis for Run 1B, motivating analysis choices informed by details specific to this run., Comment: 17 pages, 17 figures

A report on the progress on the high resolution data analysis of the ADMX experimental results is presented. In this paper, tools are developed and tested on a blind injection mimicking a Maxwellian like signal in the frequency domain. This blind injection will be used as a test bed which can be later implemented on all the high resolution data. The high resolution data is stored in the Fermilab server. In this analysis a PostgreSQL query was made to ensure the blind injection is in the middle of the frequency spectrum and 19 such files were found. The time series data is read using a c++ program. An apodization function is applied on the time series data and zero filled to reduce the frequency spacing in order to achieve a better interpolation. A FFTW header is used to compute the Fourier transform of the time series data. A Savitzky–Golay filter is applied on the unnormalized power which then can be used to remove the spectral shape. Each frequency spectrum has a bandwidth of 50 kHz.

In Cellular or mobile network Device to Device communication is used to reduce the burden on the root network and increase the spectral efficiency by proper utilization of the available resources. Distance and Energy Aware Device to Device communication uses an innovative technique termed as K-means algorithm along with the concept of residual energy in the user equipment’s to form the cluster and the cluster head. After each round of data transfer from the user equipment to the cluster head the residual energy in each user equipment along with the cluster head is calculated for further selection of cluster head in each cluster. In this paper while forming the network both distance and energy is considered for evaluation purpose and thus the MATLAB simulation results give an improved achievement as compared to the already existing network protocols.

The $\mu$eV axion is a well-motivated extension to the standard model. The Axion Dark Matter eXperiment (ADMX) collaboration seeks to discover this particle by looking for the resonant conversion of dark-matter axions to microwave photons in a strong magnetic field. In this Letter, we report results from a pathfinder experiment, the ADMX "Sidecar," which is designed to pave the way for future, higher mass, searches. This testbed experiment lives inside of and operates in tandem with the main ADMX experiment. The Sidecar experiment excludes masses in three widely spaced frequency ranges (4202-4249, 5086-5799, and 7173-7203 MHz). In addition, Sidecar demonstrates the successful use of a piezoelectric actuator for cavity tuning. Finally, this publication is the first to report data measured using both the TM$_{010}$ and TM$_{020}$ modes., Comment: 7 Pages, 4 figures

Context: The rapid spread of COVID-19 globally continues to be a threat for healthcare professionals. Dental students and practitioners remain at the risk of having this disease. Aim: The aim of this survey was to assess the knowledge, attitude, and perception of dental students across India toward COVID-19. Settings and Design: A survey with 51 questions to obtain knowledge, attitude, and perception of dental students toward COVID-19 was formulated, pretested via a pilot study and then validated. Subjects and Methods: The final questionnaire was circulated through a link to Google forms, making participation voluntary. Statistical Analysis Used: Statistical analysis was carried out using one-way analysis of variance (ANOVA) test and independent t-test. Results: A total of 610 undergraduate dental students (3rd year, 4th year and students undergoing internship) from various dental colleges across the country responded. On intergroup comparison using One-way ANOVA test, between knowledge, attitude, and perception of dental undergraduate students, attitude toward COVID-19 was found be of statistical significance with P = 0.008. Conclusion: Knowledge, awareness, and perception toward COVID-19 will help contain the spread of this infectious disease that can be caused during dental procedures. There lies a strong call to conduct educational programs on COVID-19 regarding the infection control practices for all healthcare professions, especially dental school students.

This Letter reports results from a haloscope search for dark matter axions with masses between 2.66 and 2.81 $\mu$eV. The search excludes the range of axion-photon couplings predicted by plausible models of the invisible axion. This unprecedented sensitivity is achieved by operating a large-volume haloscope at sub-kelvin temperatures, thereby reducing thermal noise as well as the excess noise from the ultra-low-noise SQUID amplifier used for the signal power readout. Ongoing searches will provide nearly definitive tests of the invisible axion model over a wide range of axion masses., Comment: 5 pages, 4 figures

A Pound reflection locking method is used to tune to a desired frequency high-Q microwave resonant cavities to be used for axion detection. A phase-modulated RF signal is fed to the cavity and the reflected RF signal is detected with a zero-bias Schottky diode detector. The detected signal is analyzed using a lock-in amplifier synchronized to the phase modulation frequency. The lock-in output is integrated and amplified to provide the feedback signal to a servomechanism to lock the resonant cavity to the desired frequency.

Dengue viral infection with unusual presentations has been described in literature, but autopsy is rarely done and is only limited to some cases, based on the literature review. Here, we present the autopsy findings in three cases of dengue encephalitis. All the three patients clinically presented with signs of meningoencephalitis and were positive for dengue non-structural (NS) 1 antigen (Ag) in the serum and cerebrospinal fluid. The postmortem findings revealed cerebral edema, inflammation, hemorrhage, and microinfarcts in all the three cases with herniation of the brain in one case. Sub-massive hepatocellular necrosis was seen in one case. The renal findings included hemorrhage into the Bowman's capsule with red cell cast in two of three cases. The pulmonary findings included a diffuse destruction of the alveoli and hemorrhage into the alveolar spaces in all the three cases.

The conformation of the synthetic cyclic tetrapeptide cyclo(D-Phe-Pro-Sar-Gly) has been determined in solution using the nuclear magnetic resonance technique and in the crystal state by X-ray crystallography. Results showed that the peptide exhibited two different conformations in solution, conformer 1 having cis-trans-cis-trans peptide bonds and conformer 2 having trans-cis-trans-cis peptide bonds. No intramolecular hydrogen bonds were observed in the structures. The X-ray diffraction studies showed the crystals to be orthorhombic with space group P2(1)2(1)2(1) with unit-cell dimensions, a = 5.790, b = 10.344, c = 31.446 A, Z = 4, R = 0.104 for 2301 observed reflections. The crystal structure showed only one type of conformer having cis-trans-cis-trans peptide bonds similar to the conformer 1 in solution.

Crystal structures of two different forms of the calcium perchlorate complex of cyclo(Ala-Leu-Pro-Gly)2 have been determined and refined using X-ray crystallographic techniques. Orthorhombic form: C32H52N8O8.Ca(ClO4)2.7H2O.2CH3OH, space group C222(1), a = 14.366, b = 18.653, c = 19.824 A, Z = 4, R = 0.068 for 2208 observed reflections. Monoclinic form: C32H52N8O8.Ca(ClO4)2.4H2O, space group C2, a = 21.096, b = 10.182, c = 11.256 A, beta = 103.33 degrees, Z = 2, R = 0.075 for 2165 observed reflections. The cyclic peptide molecule in both the structures has the form of a twofold symmetric, slightly elongated bowl. Type II' beta-turns, involving Gly and Ala at the corners, exist at the two ends of the molecule. The interior of the molecule is substantially hydrophilic, and the external surface of the bowl is largely hydrophobic. The calcium ion is located at the centre of the mouth of the bowl-like molecule. In both crystal forms, four peptide carbonyl oxygens from the cyclic peptide and two solvent oxygens coordinate to the metal ion. The mode of complexation may be described as incomplete encapsulation as, for example, in the case of metal complexes of antamanide. In the crystal structures the complex ions are held together by hydrogen bonds involving perchlorate ions and water molecules. The molecular structure observed in the crystals is entirely consistent with the results of solution studies, which also indicate the conformation of the cyclic peptide in the complex to be similar to that of the uncomplexed molecule.

Studies in a Shock Tube for Recording of Optimal Spectrum

This research work discusses a file-type-independent cryptosystem using the conversion of Cartesian and Polar coordinate systems in three dimensions. This is an advancement to PythoCrypt (IJESM, Vol-3,Issue-2, 48-51,2013) where a new algorithm was discussed that can be effectively used to provide security to medical images (IEEE, Proceedings of ICe-HNAS-9, 244 – 247, 2007) or files that have a small region or block of interest (JMBE, Vol- 27, Issue-3,144-149, 2007)(Springer.Link, FAW-1 proceedings, 62-73,2007). The usage of geometrical objects for encryption is still young and an attempt was made to employ an enhanced method of PythoCrypt to encrypt different file types. The present research work explores the inter-operability of the two coordinate systems as a basis for a cryptosystem. The work proposes a crypto-system with considerable security with one requirement; the use of a secure channel for key exchange.

The quasi-random model of molecular band absorption is used to study the interaction of a dye laser beam, tuned to 575 nm, with the absorption lines of nitrogen. Values of transmittance, averaged over intervals of 0.2 cm−1, are obtained for absorber thickness 0.2 and 10 atmosphere centimeters in the frequency interval 17,386–17,397 cm−1. From these values, intensities of the absorption lines in the first positive system of N2 are simulated.

Several major histocompatibility complex class II (MHC II) complexes with known minimal immunogenic peptides have now been solved by X-ray crystallography. Specificity pockets within the MHC II binding groove provide distinct peptide contacts that influence peptide conformation and define the binding register within different allelic MHC II molecules. Altering peptide ligands with respect to the residues that contact the T-cell receptor (TCR) can drastically change the nature of the ensuing immune response. Here, we provide an example of how MHC II (I-A) molecules may indirectly effect TCR contacts with a peptide and drive functionally distinct immune responses. We modeled the same immunogenic 12-amino acid peptide into the binding grooves of two allelic MHC II molecules linked to distinct cytokine responses against the peptide. Surprisingly, the favored conformation of the peptide in each molecule was distinct with respect to the exposure of the N- or C-terminus of the peptide above the MHC II binding groove. T-cell clones derived from each allelic MHC II genotype were found to be allele-restricted with respect to the recognition of these N- vs. C-terminal residues on the bound peptide. Taken together, these data suggest that MHC II alleles may influence T-cell functions by restricting TCR access to specific residues of the I-A-bound peptide. Thus, these data are of significance to diseases that display genetic linkage to specific MHC II alleles, e.g. type 1 diabetes and rheumatoid arthritis.

The objective of this study was to evaluate the relationship between conformational flexibility and solution stability of a linear RGD peptide (Arg-Gly-Asp-Phe-OH; 1) and a cyclic RGD peptide (cyclo-(1, 6)-Ac-Cys-Arg-Gly-Asp-Phe-Pen-NH2; 2); as a function of pH. Previously, it was found that cyclic peptide 2 was 30-fold more stable than linear peptide 1. Therefore, this study was performed to explain the increase in chemical stability based on the preferred conformation of the peptides. Molecular dynamics simulations and energy minimizations were conducted to evaluate the backbone flexibility of both peptides under simulated pH conditions of 3, 7 and 10 in the presence of water. The reactive sites for degradation for both molecules were also followed during the simulations. The backbone of linear peptide 1 exhibited more flexibility than that of cyclic peptide 2, which was reflected in the rotation about the phi and psi dihedral angles. This was further supported by the low r.m.s. deviations of the backbone atoms for peptide 2 compared with those of peptide 1 that were observed among structures sampled during the molecular dynamics simulations. The presence of a salt bridge between the side chain groups of the Arg and Asp residues was also indicated for the cyclic peptide under simulated conditions of neutral pH. The increase in stability of the cyclic peptide 2 compared with the linear peptide 1, especially at neutral pH, is due to decreased structural flexibility imposed by the ring, as well as salt bridge formation between the side chains of the Arg and Asp residues in cyclic peptide 2. This rigidity would prevent the Asp side chain carboxylic acid from orienting itself in the appropriate position for attack on the peptide backbone.

The purpose of this study is to elucidate the solution conformation of cyclic peptide 1 (cIBR), cyclo (1, 12)-Pen1-Pro2-Arg3-Gly4-Gly5-Ser6-Val7-Leu8-V al9-Thr10-Gly11-Cys12-OH, using NMR, circular dichroism (CD) and molecular dynamics (MD) simulation experiments. cIBR peptide (1), which is derived from the sequence of intercellular adhesion molecule-1 (ICAM-1, CD54), inhibits homotypic T-cell adhesion in vitro. The peptide hinders T-cell adhesion by inhibiting the leukocyte function-associated antigen-1 (LFA-1, CD11a/CD18) interaction with ICAM-1. Furthermore, Molt-3 T cells bind and internalize this peptide via cell surface receptors such as LFA-1. Peptide internalization by the LFA-1 receptor is one possible mechanism of inhibition of T-cell adhesion. The recognition of the peptide by LFA-1 is due to its sequence and conformation; therefore, this study can provide a better understanding for the conformational requirement of peptide-receptor interactions. The solution structure of 1 was determined using NMR, CD and MD simulation in aqueous solution. NMR showed a major and a minor conformer due to the presence of cis/trans isomerization at the X-Pro peptide bond. Because the contribution of the minor conformer is very small, this work is focused only on the major conformer. In solution, the major conformer shows a trans-configuration at the Pen1-Pro2 peptide bond as determined by HMQC NMR. The major conformer shows possible beta-turns at Pro2-Arg3-Gly4-Gly5, Gly5-Ser6-Val7-Leu8, and Val9-Thr10-Gly11-Cys12. The first beta-turn is supported by the ROE connectivities between the NH of Gly4 and the NH of Gly5. The connectivities between the NH of Ser6 and the NH of Val7, followed by the interaction between the amide protons of Val7 and Leu8, support the presence of the second beta-turn. Furthermore, the presence of a beta-turn at Val9-Thr10-Gly11-Cys12 is supported by the NH-NH connectivities between Thr10 and Gly11 and between Gly11 and Cys12. The propensity to form a type I beta-turn structure is also supported by CD spectral analysis. The cIBR peptide (1) shows structural similarity at residues Pro2 to Val7 with the same sequence in the X-ray structure of D1-domain of ICAM-1. The conformation of Pro2 to Val7 in this peptide may be important for its binding selectivity to the LFA-1 receptor.

Background: Oral Lichen Planus (OLP) is considered to be associated with numerous systemic conditions one of which includes Chronic Liver Disease (CLD). Hepatitis virus B and C (HBV and HCV) have known to be important causative agents of CLD and can be prevalent in asymptomatic carriers that can make them difficult to identify. Off late, the association of viral hepatitis with OLP has been a subject of controversy due to conflicting reports. Indian studies on this regard are sparse to evaluate the same. Association between the hepatitis virus and OLP, if present and established, can be of great help to format a protocol for identifying carrier states of viral hepatitis due to HBV and HCV. Methodology: Forty five cases of clinically and histologically confirmed OLP were subjected to a serological screening of hepatitis B and C viruses by detection of hepatitis B surface antigen and anti-hepatitis C virus antibodies. Results: None of OLP cases were seropositive for the hepatitis viruses. Conclusion: We could not demonstrate any association between OLP and viral hepatitis. This could be attributed to lower prevalence of hepatitis viruses compared to the countries hyper endemic for these viruses or genotypic variation of the viruses or other etiological factors contributing for the present group of patients.

BSP proteins and their homologs are a family of structurally related proteins characterized by the presence of tandem fibronectin type II domains. In the bovine species, BSP proteins were shown to be involved in sperm capacitation, a posttesticular maturation event necessary for sperm to acquire the ability to fertilize an oocyte. Recently, many new genes from this family have been discovered in numerous mammalian species. However, inconsistency in the nomenclature is creating much confusion. In light of the rapid growth of the BSP superfamily of proteins, we propose a new nomenclature in collaboration with the HUGO Gene Nomenclature Committee.

Propagation of a dye laser beam of wavelength 5700 A through nitrogen is considered. Values of transmittance, averaged over intervals of 0.5 cm(-1), are obtained for absorber thicknesses of 0.1, 1, and 10 atm-cm, using the quasi-random model of molecular band absorption. From these values, intensities of the absorption lines in the first positive system of N(2) are simulated in the frequency interval of 17,540-17,548 cm(-1).

Neuropeptide Y (NPY), receptors belong to the G-protein coupled receptor superfamily. NPY mediates several physiological responses, such as blood pressure, food intake, sedation. These actions of NPY are mediated by six receptor subtypes denoted as Y1-Y5 and y6. Modeling of receptor subtypes and binding site identification is an important step in developing new therapeutic agents. We have attempted to model the three NPY receptor types, Y1, Y4, and Y5 using homology modeling and threading methods. The models are consistent with previously reported experimental evidence. To understand the interaction and selectivity of NPY analogues with different neuropeptide receptors, docking studies of two neuropeptide analogues (BVD10 and BVD15) with receptors Y1 and Y4 were carried out. Results of the docking studies indicated that the interaction of ligands BVD10 and BVD15 with Y1 and Y4 receptors are different. These results were evaluated for selectivity of peptide analogues BVD10 and BVD15 towards the receptors.

The interaction between cell-adhesion molecules CD2 and CD58 is critical for an immune response. Modulation or inhibition of these interactions has been shown to be therapeutically useful. Synthetic 12-mer linear and cyclic peptides, and cyclic hexapeptides based on rat CD2 protein, were designed to modulate CD2-CD58 interaction. The synthetic peptides effectively blocked the interaction between CD2-CD58 proteins as demonstrated by antibody binding, E-rosetting and heterotypic adhesion assays. NMR and molecular modeling studies indicated that the synthetic cyclic peptides exhibit beta-turn structure in solution and closely mimic the beta-turn structure of the surface epitopes of the CD2 protein. Docking studies of CD2 peptides and CD58 protein revealed the possible binding sites of the cyclic peptides on CD58 protein. The designed cyclic peptides with beta-turn structure have the ability to modulate the CD2-CD58 interaction.

Peptides and proteins are essential to many biological processes. The interaction between the peptide ligands and their receptor targets commonly involves beta-turn structures. Yet poor bioavailability and unfavorable pharmacokinetics significantly compromise the use of peptides as drugs. Thus, there has been a great deal of interest in the design of peptidomimetics (modified peptides) as therapeutic agents by mimicking beta-turn structures. This review highlights the importance of beta-turn in the design of various peptidomimetics for many diseases. This review also outlines several beta-turn mimicking strategies and its application in the design of potent peptide analogues. beta-turn mimetics often tend to be more rigid in positioning the critically important amino acid residues and thus optimize the surface conformation for productive interaction with the receptors.

The objective of this work is to evaluate the ability of peptides derived from the bulge (HAV-peptides) and groove (ADT-peptides) regions of E-cadherin EC1-domain to increase the paracellular porosity of the intercellular junctions of Madin-Darby canine kidney (MDCK) cell monolayers.Peptides were synthesized using a solid-phase method and were purified using semi-preparative HPLC. MDCK monolayers were used to evaluate the ability of cadherin peptides to modulate cadherin-cadherin interactions in the intercellular junctions. The increase in intercellular junction porosity was determined by the change in transepithelial electrical resistance (TEER) values and the paracellular transport of 14C-mannitol.HAV- and ADT-peptides can lower the TEER value of MDCK cell monolayers and enhance the paracellular permeation of 14C-mannitol. HAV- and ADT-decapeptides can modulate the intercellular junctions when they are added from the basolateral side but not from the apical side; on the other hand. HAV- and ADT-hexapeptides increase the paracellular porosity of the monolayers when added from either side. Conjugation of HAV- and ADT-peptides using omega-aminocaproic acid can only work to modulate the paracellular porosity when ADT-peptide is at the N-terminus and HAV-peptide is at the C-terminus; because of its size, the conjugate can only modulate the intercellular junction when added from the basolateral side.Peptides from the bulge and groove regions of the EC1 domain of E-cadherin can inhibit cadherin-cadherin interactions, resulting in the opening of the paracellular junctions. These peptides may be used to improve paracellular permeation of peptides and proteins. Furthermore, this work suggests that both groove and bulge regions of EC-domain are important for cadherin-cadherin interactions.

The counter receptors intercellular adhesion molecule (ICAM)-1 and lymphocyte function-associated antigen (LFA)-1 are lymphocyte cell surface adhesion proteins the interaction of which can provide signals for T cell activation. This binding event is important in T cell function, migration, and general immune system regulation. The ability to inhibit this interaction with monoclonal antibodies has proved to be therapeutically useful for several allograft rejection and autoimmune disease models.Short peptides representing counter-receptor contact domains of LFA-1 and ICAM-1 were examined for their ability to inhibit T cell adhesion and T cell function.Peptides encompassing amino acids Q1-C21 and D26-K50 of ICAM-1, I237-I261 and G441-G466 of the LFA-1 alpha-subunit, and D134-Q159 of the LFA-1 beta-subunit inhibited LFA-1/ICAM-1-dependent adhesion in a phorbol-12,13-dibutyrate-induced model of tonsil T cell homotypic adhesion. This inhibition was specific to the peptide sequence and occurred without stimulation of T cell proliferation. The peptides also were effective in preventing T cell function using a one-way mixed lymphocyte reaction model for bone marrow transplantation.Our data suggest that these peptides or their derivatives may be useful as therapeutic modulators of LFA-1/ICAM-1 interaction during organ transplants.

The objective of this study was to evaluate the relationship between conformational flexibility and solution stability of a linear RGD peptide (Arg-Gly-Asp-Phe-OH; 1) and a cyclic RGD peptide (cyclo-(1, 6)-Ac-Cys-Arg-Gly-Asp-Phe-Pen-NH2; 2); as a function of pH. Previously, it was found that cyclic peptide 2 was 30-fold more stable than linear peptide 1. Therefore, this study was performed to explain the increase in chemical stability based on the preferred conformation of the peptides. Molecular dynamics simulations and energy minimizations were conducted to evaluate the backbone flexibility of both peptides under simulated pH conditions of 3, 7 and 10 in the presence of water. The reactive sites for degradation for both molecules were also followed during the simulations. The backbone of linear peptide 1 exhibited more flexibility than that of cyclic peptide 2, which was reflected in the rotation about the phi and psi dihedral angles. This was further supported by the low r.m.s. deviations of the backbone atoms for peptide 2 compared with those of peptide 1 that were observed among structures sampled during the molecular dynamics simulations. The presence of a salt bridge between the side chain groups of the Arg and Asp residues was also indicated for the cyclic peptide under simulated conditions of neutral pH. The increase in stability of the cyclic peptide 2 compared with the linear peptide 1, especially at neutral pH, is due to decreased structural flexibility imposed by the ring, as well as salt bridge formation between the side chains of the Arg and Asp residues in cyclic peptide 2. This rigidity would prevent the Asp side chain carboxylic acid from orienting itself in the appropriate position for attack on the peptide backbone.

The absorption spectrum of the N2 molecule has been excited from high vibrational levels of the ground state by the flash discharge technique and has been photographed at a high resolution in the spectral region 1200-1330 AA. The rotational analysis of the observed band assigns the spectrum to the transition between the b'1 Sigma u+, v=0, 1, 2, 3 and 4, levels and the excited vibrational levels (v=10, 11, 12 and 13) of the ground state, X1 Sigma g+. In absorption, the v'=0 level of the b'1 Sigma u+ state is studied at high resolution for the first time. Perturbations are seen in the v'=1-4 levels of the b' state and are found to be consistent with the findings of previous workers.

Four new bands in the red region are observed which have been described in terms of A2Σ+–B2Σ+ and F2Σ+–B2Σ+ systems. A rotational analysis together with deperturbation calculation of one band at 6763 Å has shown that A2Σ+ (ν = 7) and F2Σ+ (ν = 0) vibrational levels are involved in a homogeneous perturbation. The rotational structure study of three bands of a new transition I2Σ+–A2Σ+ has been carried out. From the study of heterogeneous perturbations observed in the I vibrational levels, it has been suggested that the perturbing state is a 2Π state arising from the 3d complex.

Rotational structure of emission bands of the PO molecule in the region 5300–3800 Å is analyzed. The spectrum is attributed to 5 electronic transitions A2Σ+–B2Σ+, F2Σ+–B2Σ+, G2Σ+–B2Σ+, H2Σ+–B2Σ+, and I2Σ+–B2Σ+, where F, G, H, and I are the new electronic states and A and B are the upper states of the well-known γ and β bands respectively. Practically all the new 2Σ states are found to be perturbed. A qualitative account of these perturbations together with a deperturbation of certain levels is given. A number of cases of predissociation are also observed. This predissociation is attributed to the presence of 4Πi, and A′2Σ+ states, which dissociate to the ground state atomic products. From this an upper limit of the dissociation energy of the ground state of PO is determined to be D0 = 49 536 cm−1. The A, D, E, G, H, and I states of this molecule are assigned as Rydberg states corresponding to the σ4s, π4p, δ3d, σ4p, σ3d, and σ5s orbitals, respectively. From them a value of 67 570 cm−1 is evaluated for the first ionization potential of PO. All the electronic states established for this molecule are described in terms of electron configurations.

The Molecular Compounds of 4 :6-Dichloro-1 :3 Dinitrobenzene.