ADAPT: a price-stabilizing compliance policy for renewable energy certificates: the case of SREC markets

Currently most Renewable Energy Certificate (REC) markets are defined based on targets which create an artificial step demand function resembling a cliff. This target policy produces volatile prices which can make investing in renewables a risky proposition. In this paper, we propose an alternative policy called Adjustable Dynamic Assignment of Penalties and Targets (ADAPT) which uses a sloped compliance penalty and a self-regulating requirement schedule, both designed to stabilize REC prices, helping to alleviate a common weakness of environmental markets. To capture market behavior, we model the market as a stochastic dynamic programming problem to understand how the market might balance the decision to use a REC now versus holding it for future periods (in the face of uncertain new supply). Then, we present and prove some of the properties of this market, and finally we show that this mechanism reduces the volatility of REC prices which should stabilize the market and encourage long-term investment in renewables

Spinal cord molecular and cellular changes induced by adenoviral vector- and cell-mediated triple gene therapy after severe contusion

© 2017 Izmailov, Povysheva, Bashirov, Sokolov, Fadeev, Garifulin, Naroditsky, Logunov, Salafutdinov, Chelyshev, Islamov and Lavrov. The gene therapy has been successful in treatment of spinal cord injury (SCI) in several animal models, although it still remains unavailable for clinical practice. Surprisingly, regardless the fact that multiple reports showed motor recovery with gene therapy, little is known about molecular and cellular changes in the post-traumatic spinal cord following viral vector- or cell-mediated gene therapy. In this study we evaluated the therapeutic efficacy and changes in spinal cord after treatment with the genes encoding vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF), angiogenin (ANG), and neuronal cell adhesion molecule (NCAM) applied using both approaches. Therapeutic genes were used for viral vector- and cell-mediated gene therapy in two combinations: (1) VEGF+GDNF+NCAM and (2) VEGF+ANG+NCAM. For direct gene therapy adenoviral vectors based on serotype 5 (Ad5) were injected intrathecally and for cell-mediated gene delivery human umbilical cord blood mononuclear cells (UCB-MC) were simultaneously transduced with three Ad5 vectors and injected intrathecally 4 h after the SCI. The efficacy of both treatments was confirmed by improvement in behavioral (BBB) test. Molecular and cellular changes following post-traumatic recovery were evaluated with immunofluorescent staining using antibodies against the functional markers of motorneurons (Hsp27, synaptophysin, PSD95), astrocytes (GFAP, vimentin), oligodendrocytes (Olig2, NG2, Cx47) and microglial cells (Iba1). Our results suggest that both approaches with intrathecal delivery of therapeutic genes may support functional recovery of post-traumatic spinal cord via lowering the stress (down regulation of Hsp25) and enhancing the synaptic plasticity (up regulation of PSD95 and synaptophysin), supporting oligodendrocyte proliferation (up regulation of NG2) and myelination (up regulation of Olig2 and Cx47), modulating astrogliosis by reducing number of astrocytes (down regulation of GFAP and vimetin) and microglial cells (down regulation of Iba1)

Прогноз в области создания вакцин нового поколения для вакцинопрофилактики и вакцинотерапии инфекционных и неинфекционных болезней

.

rAAV expressing recombinant antibody for emergency prevention and long-term prophylaxis of COVID-19

IntroductionNumerous agents for prophylaxis of SARS-CoV-2-induced diseases are currently registered for the clinical use. Formation of the immunity happens within several weeks following vaccine administration which is their key disadvantage. In contrast, drugs based on monoclonal antibodies, enable rapid passive immunization and therefore can be used for emergency pre- and post-exposure prophylaxis of COVID-19. However rapid elimination of antibody-based drugs from the circulation limits their usage for prolonged pre-exposure prophylaxis.MethodsIn current work we developed a recombinant adeno-associated viral vector (rAAV), expressing a SARS-CoV-2 spike receptor-binding domain (RBD)-specific antibody P2C5 fused with a human IgG1 Fc fragment (P2C5-Fc) using methods of molecular biotechnology and bioprocessing.Results and discussionsA P2C5-Fc antibody expressed by a proposed rAAV (rAAV-P2C5-Fc) was shown to circulate within more than 300 days in blood of transduced mice and protect animals from lethal SARS-CoV-2 virus (B.1.1.1 and Omicron BA.5 variants) lethal dose of 105 TCID50. In addition, rAAV-P2C5-Fc demonstrated 100% protective activity as emergency prevention and long-term prophylaxis, respectively. It was also demonstrated that high titers of neutralizing antibodies to the SARS-CoV-2 virus were detected in the blood serum of animals that received rAAV-P2C5-Fc for more than 10 months from the moment of administration.Our data therefore indicate applicability of an rAAV for passive immunization and induction of a rapid long-term protection against various SARS-CoV-2 variants

ВОЗМОЖНО ЛИ ВЛИЯНИЕ МИКОПЛАЗМЕННОЙ ИНФЕКЦИИ НА ПАТОГЕНЕЗ РАКА ПРЕДСТАТЕЛЬНОЙ ЖЕЛЕЗЫ?

Objective: to define a possible correlation between Mycoplasma infection persistence and prostate cancer (PC). Subjects and methods. Two hundred and fifty males aged 45 to 83 years (mean age 65.50.71 years) with suspected PC were examined. In all the patients, polyfocal prostate biopsy from 12 points was carried out, by additionally taking 2 tissue columns from the peripheral area of both lobes. The basic material was referred for morphological study; the two additional columns were tested for Mycoplasma DNA by a polymerase chain reaction (PCR) and real-time PCR. The study was blind. According to the morphological findings, the patients were divided into 2 groups: 1) those with chronic prostatitis, prostate adenoma, low-grade prostatic interstitial neoplasia (PIN); 2) those with high-grade PIN (HG-PIN), PC. There were no age differences between the groups (p = 0.05). Results. The standard procedure for PCR was applied to 127 subjects. Twenty-six (20.5%) of the 127 subjects with suspected PC were found to have Mycoplasma infection, Mycoplasma being detected in 21 (26.2%) of the 81 patients with verified HG-PIN and PC. Mycoplasma hominis was encountered in 19 (15%) patients of the 127 subjects with suspected PC and this infection was present in 16 (20%) of the 81 patients with verified HG-PIN and PC. Comparison of the frequency of HG-PIN and PC in the patients of general group (60%) and in those with Mycoplasma infection (80.8%) revealed significant differences (p = 0.031). HG-PIN and PC were also significantly more frequently seen in the patients with Mycoplasma hominis (84.2%) that in the general patient group (60%) (p = 0.033). There were no significant differences in the frequency of HG-PIN and PC between the patients from the general group (60%) and those with Mycoplasma genitalium (71.4%) (p = 0.05). The patients with verified PC and HG-PIN were more frequently found to have Mycoplasma hominis (20%) than Mycoplasma genitalium (6.2%), which further drew our closer attention to just this pathogen. The real-time PCR was used in 123 subjects to detect Mycoplasma. HG-PIN and prostate adenocarcinoma were revealed in 63 of the 123 patients with suspected PC, Mycoplasma hominis was seen in 46 (37%). The frequency (n=46) was 73.9%. The frequency of HG-PIN and PC was significantly higher in the patients with isolated Mycoplasma hominis DNA that in those without this pathogen (p < 0.001). Conclusion. Thus, the investigation showed a significantly higher correlation in the frequency of HG-PIN and PC in the patients with Mycoplasma infection that in the general study patients with suspected PC. This was supported by the use of both the standard procedure for Mycoplasma DNA determination and real-time PCR diagnosis.Objective: to define a possible correlation between Mycoplasma infection persistence and prostate cancer (PC). Subjects and methods. Two hundred and fifty males aged 45 to 83 years (mean age 65.50.71 years) with suspected PC were examined. In all the patients, polyfocal prostate biopsy from 12 points was carried out, by additionally taking 2 tissue columns from the peripheral area of both lobes. The basic material was referred for morphological study; the two additional columns were tested for Mycoplasma DNA by a polymerase chain reaction (PCR) and real-time PCR. The study was blind. According to the morphological findings, the patients were divided into 2 groups: 1) those with chronic prostatitis, prostate adenoma, low-grade prostatic interstitial neoplasia (PIN); 2) those with high-grade PIN (HG-PIN), PC. There were no age differences between the groups (p = 0.05). Results. The standard procedure for PCR was applied to 127 subjects. Twenty-six (20.5%) of the 127 subjects with suspected PC were found to have Mycoplasma infection, Mycoplasma being detected in 21 (26.2%) of the 81 patients with verified HG-PIN and PC. Mycoplasma hominis was encountered in 19 (15%) patients of the 127 subjects with suspected PC and this infection was present in 16 (20%) of the 81 patients with verified HG-PIN and PC. Comparison of the frequency of HG-PIN and PC in the patients of general group (60%) and in those with Mycoplasma infection (80.8%) revealed significant differences (p = 0.031). HG-PIN and PC were also significantly more frequently seen in the patients with Mycoplasma hominis (84.2%) that in the general patient group (60%) (p = 0.033). There were no significant differences in the frequency of HG-PIN and PC between the patients from the general group (60%) and those with Mycoplasma genitalium (71.4%) (p = 0.05). The patients with verified PC and HG-PIN were more frequently found to have Mycoplasma hominis (20%) than Mycoplasma genitalium (6.2%), which further drew our closer attention to just this pathogen. The real-time PCR was used in 123 subjects to detect Mycoplasma. HG-PIN and prostate adenocarcinoma were revealed in 63 of the 123 patients with suspected PC, Mycoplasma hominis was seen in 46 (37%). The frequency (n=46) was 73.9%. The frequency of HG-PIN and PC was significantly higher in the patients with isolated Mycoplasma hominis DNA that in those without this pathogen (p < 0.001). Conclusion. Thus, the investigation showed a significantly higher correlation in the frequency of HG-PIN and PC in the patients with Mycoplasma infection that in the general study patients with suspected PC. This was supported by the use of both the standard procedure for Mycoplasma DNA determination and real-time PCR diagnosis

Safety and immunogenicity of rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine against SARS-CoV-2 in healthy adolescents: an open-label, non-randomized, multicenter, phase 1/2, dose-escalation study

To protect young individuals against SARS-CoV-2 infection, we conducted an open-label, prospective, non-randomised dose-escalation Phase 1/2 clinical trial to evaluate the immunogenicity and safety of the prime-boost “Sputnik V” vaccine administered at 1/10 and 1/5 doses to adolescents aged 12–17 years. The study began with the vaccination of the older cohort (15-to-17-year-old participants) with the lower (1/10) dose of vaccine and then expanded to the whole group (12-to-17-year-old participants). Next, 1/5 dose was used according to the same scheme. Both doses were well tolerated by all age groups. No serious or severe adverse events were detected. Most of the solicited adverse reactions were mild. No significant differences in total frequencies of adverse events were registered between low and high doses in age-pooled groups (69.6% versus 66.7%). In contrast, the 1/5 dose induced significantly higher humoral and T cell-mediated immune responses than the 1/10 dose. The 1/5 vaccine dose elicited higher antigen-binding (both S and RBD-specific) as well as virus-neutralising antibody titres at the maximum of response (day 42), also resulting in a statistically significant difference at a distanced timepoint (day 180) compared to the 1/10 vaccine dose. Higher dose resulted in increased cross-neutralization of Delta and Omicron variants.;Clinical Trial RegistrationClinicalTrials.gov, NCT04954092, LP-007632

Analysis of the genome of type 7 simian adenovirus using restrictases.

The effect of the restricting endonucleases R.EcoRI, R.BamI and R.SalI on the genome of type 7 simian adenovirus (SA-7) has been studied. Since the DNA has only one site of R.EcoRI recognition the enzyme cleaves SA-7 DNA into two fragments with the molecular weights 12.0 and 10.0 . 10(6). The restrictase R.BamI cleaves the SA-7 DNA at six sites producing 7 fragments with the molecular weights 6.6, 5.9, 3.8, 2.7, 1.3, 0.7 and 0.6 . 10(6). R.SalI cleavage yields 6 fragments with the molecular weights 8.1, 5.5, 4.3, 2.45, 1.2 and 0.6 . 10(6). The R.BamI and R.SalI fragments are arranged in the orders E-A-D-F-C-G-B and A-B-D-F-E-C, respectively. The only R.EcoRI recognition site is localized in the C fragment produced by R.BamI and in the B fragment produced by R.SalI