In-depth proteomics and glycoproteomics by mass spectrometry and affinity-based platforms for selectively capturing proteins and glycoproteins from breast cancer and disease free human serum

Scope and Method of Study:The major purpose of the work presented in this dissertation is to contribute to the introduction and evaluation of new ways and strategies for reducing the complexity of human serum and in turn contribute to facilitating the identification of candidate biomarkers with the assistance of advanced mass spectrometry techniques. In one approach, immobilized metal affinity chromatography (IMAC) and protein equalizer techniques were combined to reduce the complexity of the human serum. In another approach, lectin affinity chromatography involving tandem lectin columns with narrow and broad specificity lectins were evaluated in the selective enrichment of the glycoproteins present in human serum.Findings and Conclusions:The investigation described in this dissertation has significantly contributed to the in-depth proteomics analysis of human serum. The equalization/IMAC strategy allowed the identification of 82 non-redundant proteins, which was facilitated by the IMAC postfractionation process after equalization. The tandem-lectin affinity based platforms developed in this investigation selectively captured glycoproteins from breast cancer serum and disease-free serum and many proteins that were differentially expressed in the cancer serum were identified. In a platform where a combination of broad and narrow specificity lectins were evaluated in tandem series, 165 non-redundant proteins were identified. The platforms developed in this investigation are expected to be of general use and to facilitate the identification of additional candidate biomarkers for various diseases in the future

Epidemiology of Untreated Psychoses in 3 Diverse Settings in the Global South: The International Research Program on Psychotic Disorders in Diverse Settings (INTREPID II)

IMPORTANCE: Less than 10% of research on psychotic disorders has been conducted in settings in the Global South, which refers broadly to the regions of Latin America, Asia, Africa, and Oceania. There is a lack of basic epidemiological data on the distribution of and risks for psychoses that can inform the development of services in many parts of the world. OBJECTIVE: To compare demographic and clinical profiles of cohorts of cases and rates of untreated psychoses (proxy for incidence) across and within 3 economically and socially diverse settings in the Global South. Two hypotheses were tested: (1) demographic and clinical profiles of cases with an untreated psychotic disorder vary across setting and (2) rates of untreated psychotic disorders vary across and within setting by clinical and demographic group. DESIGN, SETTING, AND PARTICIPANTS: The International Research Program on Psychotic Disorders in Diverse Settings (INTREPID II) comprises incidence, case-control, and cohort studies of untreated psychoses in catchment areas in 3 countries in the Global South: Kancheepuram District, India; Ibadan, Nigeria; and northern Trinidad. Participants were individuals with an untreated psychotic disorder. This incidence study was conducted from May 1, 2018, to July 31, 2020. In each setting, comprehensive systems were implemented to identify and assess all individuals with an untreated psychosis during a 2-year period. Data were analyzed from January 1 to May 1, 2022. MAIN OUTCOMES AND MEASURES: The presence of an untreated psychotic disorder, assessed using the Schedules for Clinical Assessment in Neuropsychiatry, which incorporate the Present State Examination. RESULTS: Identified were a total of 1038 cases, including 64 through leakage studies (Kancheepuram: 268; median [IQR] age, 42 [33-50] years; 154 women [57.5%]; 114 men [42.5%]; Ibadan: 196; median [IQR] age, 34 [26-41] years; 93 women [47.4%]; 103 men [52.6%]; Trinidad: 574; median [IQR] age, 30 [23-40] years; 235 women [40.9%]; 339 men [59.1%]). Marked variations were found across and within settings in the sex, age, and clinical profiles of cases (eg, lower percentage of men, older age at onset, longer duration of psychosis, and lower percentage of affective psychosis in Kancheepuram compared with Ibadan and Trinidad) and in rates of untreated psychosis. Age- and sex-standardized rates of untreated psychoses were approximately 3 times higher in Trinidad (59.1/100 000 person-years; 95% CI, 54.2-64.0) compared with Kancheepuram (20.7/100 000 person-years; 95% CI, 18.2-23.2) and Ibadan (14.4/100 000 person-years; 95% CI, 12.3-16.5). In Trinidad, rates were approximately 2 times higher in the African Trinidadian population (85.4/100 000 person-years; 95% CI, 76.0-94.9) compared with the Indian Trinidadian (43.9/100 000 person-years; 95% CI, 35.7-52.2) and mixed populations (50.7/100 000 person-years; 95% CI, 42.0-59.5). CONCLUSIONS AND RELEVANCE: This analysis adds to research that suggests that core aspects of psychosis vary by historic, economic, and social context, with far-reaching implications for understanding and treatment of psychoses globally

Eumelanin-Inspired Core Derived From Vanillin: A New Building Block for Organic Semiconductors

An eumelanin-inspired core derived from the natural product, vanillin (vanilla bean extract) was utilized for the synthesis of eumelanin-inspred small molecules and polymer via Sonogashira cross coupling. The materials demonstrate that the methyl 4,7-dibromo-5,6-dimethoxy-N-methyl-1H-indole-2-carboxylate core can serve as a new building block for organic semiconductors

Application of Deep Learning to the Prediction of Solar Irradiance through Missing Data

The task of predicting solar irradiance is critical in the development of renewable energy sources. This research is aimed at predicting the photovoltaic plant’s irradiance or power and serving as a standard for grid stability. In practical situations, missing data can drastically diminish prediction precision. Meanwhile, it is tough to pick an appropriate imputation approach before modeling because of not knowing the distribution of datasets. Furthermore, not all datasets benefit equally from using the same imputation technique. This research suggests utilizing a recurrent neural network (RNN) equipped with an adaptive neural imputation module (ANIM) to estimate direct solar irradiance when some data is missing. Without imputed information, the typical projects’ imminent 4-hour irradiance depends on gaps in antique climatic and irradiation records. The projected model is evaluated on the widely available information by simulating missing data in each input series. The performance model is assessed alternative imputation techniques under a range of missing rates and input parameters. The outcomes prove that the suggested methods perform better than competing strategies when measured by various criteria. Moreover, combine the methodology with the attentive mechanism and invent that it excels in low-light conditions

Evaluation of New Dihydrophthalazine-Appended 2,4-Diaminopyrimidines against Bacillus anthracis: Improved Syntheses Using a New Pincer Complex

The synthesis and evaluation of ten new dihydrophthalazine-appended 2,4-diaminopyrimidines as potential drugs to treat Bacillus anthracis is reported. An improved synthesis utilizing a new pincer catalyst, dichlorobis[1-(dicyclohexylphosphanyl)-piperidine]palladium(II), allows the final Heck coupling to be performed at 90 °C using triethylamine as the base. These milder conditions have been used to achieve improved yields for new and previously reported substrates with functional groups that degrade or react at the normal 140 °C reaction temperature. An analytical protocol for separating the S and R enantiomers of two of the most active compounds is also disclosed. Finally, the X-ray structure for the most active enantiomer of the lead compound, (S)-RAB1, is given