Determination of Second Virial Coefficient of Proteins Using a Dual-Detector Cell for Simultaneous Measurement of Scattered Light Intensity and Concentration in SEC-HPLC

AbstractA method is proposed for the measurement of the B22 value of proteins in aqueous solutions in flow-mode that utilizes a novel fabricated dual-detector cell, which simultaneously measures protein concentration and the corresponding scattered light intensity at 90°, after the protein elutes from a size-exclusion column. Each data point on the chromatograms obtained from the light scattering detector and the concentration (ultraviolet) detector is converted to Rayleigh’s ratio, Rθ, and concentration, c, respectively. The B22 value is calculated from the slope of the Debye plot (Kc/Rθ versus c) generated from a range of concentrations obtained from these chromatograms for a single protein injection. It is shown that this method provides reliable determination of the B22 values for such proteins as lysozyme, chymotrypsinogen, and chymotrypsin in various solution conditions that agree well with those reported in literature

Comparative Evaluation of Clinical Efficacy of Diode LASER and Cryosurgery for Gingival Pigmentation: A Split-Mouth Randomized Clinical Study

Objective: To compare and evaluate the clinical efficacy of diode laser and cryosurgery for treating melanin pigmentation of gingiva. Material and Methods: A total of twenty-five subjects with physiological gingival pigmentation on the facial aspect of both maxillary and mandibular anterior arches (50 sites), both male and female, with an average age ranging from 18-35 years, participated in the study. The sites were randomly divided into Group I: depigmentation by Laser and Group II: depigmentation by Cryosurgery. The following parameters were assessed for the evaluation of treatment results: Melanin Oral Pigmentation Index (PI), Visual Analogue Scale (VAS) for pain evaluation and Healing index (HI). The data collected was statistically evaluated. Results: On intergroup comparison, there was no statistical difference in the score from baseline (p>0.05); however, a statistically significant difference was seen at the end of 1 year (p<0.05). Moreover, 57-60% of arches showed recurrence of pigmentation in the laser group whereas; only 12.7-17% recurrence was seen in the cryosurgery group at the end of the first year. Conclusion: Treatment of gingival hyperpigmentation with laser and cryosurgery shows a marked improvement of gingival pigmentation in both groups, but the cryosurgery depigmentation sites showed more sustainability.&nbsp

Comparative Evaluation of Clinical Efficacy of Diode LASER and Cryosurgery for Gingival Pigmentation: A Split-Mouth Randomized Clinical Study

Objective: To compare and evaluate the clinical efficacy of diode laser and cryosurgery for treating melanin pigmentation of gingiva. Material and Methods: A total of twenty-five subjects with physiological gingival pigmentation on the facial aspect of both maxillary and mandibular anterior arches (50 sites), both male and female, with an average age ranging from 18-35 years, participated in the study. The sites were randomly divided into Group I: depigmentation by Laser and Group II: depigmentation by Cryosurgery. The following parameters were assessed for the evaluation of treatment results: Melanin Oral Pigmentation Index (PI), Visual Analogue Scale (VAS) for pain evaluation and Healing index (HI). The data collected was statistically evaluated. Results: On intergroup comparison, there was no statistical difference in the score from baseline (p>0.05); however, a statistically significant difference was seen at the end of 1 year (p<0.05). Moreover, 57-60% of arches showed recurrence of pigmentation in the laser group whereas; only 12.7-17% recurrence was seen in the cryosurgery group at the end of the first year. Conclusion: Treatment of gingival hyperpigmentation with laser and cryosurgery shows a marked improvement of gingival pigmentation in both groups, but the cryosurgery depigmentation sites showed more sustainability.

BLOOM: A 176B-Parameter Open-Access Multilingual Language Model

Large language models (LLMs) have been shown to be able to perform new tasks based on a few demonstrations or natural language instructions. While these capabilities have led to widespread adoption, most LLMs are developed by resource-rich organizations and are frequently kept from the public. As a step towards democratizing this powerful technology, we present BLOOM, a 176B-parameter open-access language model designed and built thanks to a collaboration of hundreds of researchers. BLOOM is a decoder-only Transformer language model that was trained on the ROOTS corpus, a dataset comprising hundreds of sources in 46 natural and 13 programming languages (59 in total). We find that BLOOM achieves competitive performance on a wide variety of benchmarks, with stronger results after undergoing multitask prompted finetuning. To facilitate future research and applications using LLMs, we publicly release our models and code under the Responsible AI License

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival