Screening Anti-PD-L2 Peptides as Antitumor Ligands Using Phage Display

Cancer still remains one of the top leading causes of death in America. Recently, programmed cell death protein 1 (PD-1) blockades have been demonstrated to be highly effective against various types of cancer. By blocking PD-1 from binding with their ligands (PD-L1 and PD-L2), the “off” signal to the immune system is inhibited, hence reinvigorating the immune cells to kill tumor cells. To date, despite PD-L1 and PD-L2 both interacting with PD-1, research efforts have only been focused on developing anti-PD-L1 inhibitors. Therefore, the work of this honor project has focused on finding anti-PD-L2 peptides by phage display, with the purposes of expanding our cancer drug repertoire and combining anti-PD-L2 inhibitors with anti-PD-L1 drugs to achieve synergistic effects. Chapter 1 gives an overview and background of the topics that will be covered in this honor project. We will first introduce the basic principles of immune-checkpoint blockade, current treatments, challenges, our solution, and finally details of our method peptide phage display. The research detailed in chapters 2 shows initial evidence of our peptide candidates binding to PD-L2 protein using phage display, plaque assay, and ELISA test. We observed significant phage enrichment after 5 rounds of bio-panning, indicating the survival phage library has high binding ability toward PD-L2, even after harsh washing steps. We later examined this potential binding using the ELISA test. Interestingly, peptides in the latter rounds of biopanning were found to have lower binding affinity to the initial peptide input. Lastly, in chapter 3 we discuss the limitations of this study and future directions to either improve the method protocol or to select a different target

COMPARABLE GROWTH AND PRODUCTIVITY OF I. aquatica ON HYDROPONIC SUBSYSTEMS WITHIN AQUAPONIC SYSTEM

The growth and productivity of two Water Spinach varieties (Kankung Unggul BikaR and Kangkung Bangkok LP-1R) had already been experiment on two different Hydroponic culture subsystems (Floating Raft and Pumice Bed) of an Aquaponic system, where mineral nutrients of the Water Spinach vegetables were absorbed from bio-chemical processes in solid wastes of fish and excess feeds. Consequently, this study showed individual functions of these two different Hydroponic subsystems from new established dates no significant differences on the 7 date of testing. Until increasingly significant difference for the Hydroponic subsystem of Floating Raft is less effective than Hydroponic subsystem of Pumice Bed based on the length of shoot, length of petiole, width of leaf on the 14 test date and the length of shoot, length of petiole, length of leaf, the number of leaves and length of root on the 21 test date. Nonetheless, Hydroponic subsystem did not support the growth and productivity of the Water Spinach varieties in all stages of testing about statistical significance. In addition, in term of productivity and growth criteria on the 7, 14 and 21 dates of testing, no significant difference was observed between two Water Spinach varieties. Finally, the advice of this study does not reassess the treatment (Floating Raft Hydroponic subsystem and Kangkung Unggu BikaR variety) because of the poor result of length of shoot, length of petiole and reality of yield for this Kangkung Unggul BikaR variety are probably at the 21 date

Deepr: A Convolutional Net for Medical Records

Feature engineering remains a major bottleneck when creating predictive systems from electronic medical records. At present, an important missing element is detecting predictive regular clinical motifs from irregular episodic records. We present Deepr (short for Deep record), a new end-to-end deep learning system that learns to extract features from medical records and predicts future risk automatically. Deepr transforms a record into a sequence of discrete elements separated by coded time gaps and hospital transfers. On top of the sequence is a convolutional neural net that detects and combines predictive local clinical motifs to stratify the risk. Deepr permits transparent inspection and visualization of its inner working. We validate Deepr on hospital data to predict unplanned readmission after discharge. Deepr achieves superior accuracy compared to traditional techniques, detects meaningful clinical motifs, and uncovers the underlying structure of the disease and intervention space

The relationship between native Vietnamese language literacy and English language reading achievement of Vietnamese high school students /

The problem under investigation in this study was to determine whether there was a relationship between native Vietnamese language literacy and English language reading achievement of Vietnamese High School students. This research was needed in order to identify literacy in L1 is transferred and enhances reading achievement in L2. This study was focused on a group of 90 LEP Vietnamese speaking students, who attended 9th and 10th grades level in three high schools in urban public school district with the Native Language Skill Test. The median for the NLST scores was the criterion used to form two categories of cognitive literacy styles - illiterate and literate. The reading scores on the California Achievement Test (CAT) was used as the dependent variable in this study. Analysis using t-tests for two independent samples were performed to provide evidence of statistically significant differences between illiterate and literate subjects in reading scores. The reading comprehension of English story was higher for literate independent than for illiterate independent subjects. Significant differences were also found between 9th and 10th grade students, as well as for the interaction between grade and literacy levels. Results of these analyses confirmed the existence of a significantly positive relationship between the achievement of LEP students in English reading and their degree of literacy in the native language. The will to preserve the Vietnamese language is as strong as the desire to master English to perfection. Once some degree of proficiency is achieved in Vietnamese, the phenomenon of Prior Knowledge and interdependence of Learning come to play and the abilities acquired in Vietnamese can then be transferred to English

Optimal Number, Location, and Size of Distributed Generators in Distribution Systems by Symbiotic Organism Search Based Method

This paper proposes an approach based on the Symbiotic Organism Search (SOS) for optimal determining sizing, siting, and number of Distributed Generations (DG) in distribution systems. The objective of the problem is to minimize the power loss of the system subject to the equality and inequality constraints such as power balance, bus voltage limits, DG capacity limits, and DG penetration limit. The SOS approach is defined as the symbiotic relationship observed between two organisms in an ecosystem, which does not need the control parameters like other meta-heuristic algorithms in the literature. For the implementation of the proposed method to the problem, an integrated approach of Loss Sensitivity Factor (LSF) is used to determine the optimal location for installation of DG units, and SOS is used to find the optimal size of DG units. The proposed method has been tested on IEEE 33-bus, 69-bus, and 118-bus radial distribution systems. The obtained results from the SOS algorithm have been compared to those of other methods in the literature. The simulated results have demonstrated that the proposed SOS method has a very good performance and effectiveness for the problem of optimal placement of DG units in distribution systems

The role of the insula in heart rate variability

Des preuves cumulatives soutiennent le rôle de l'insula dans la régulation autonomique cardiaque et son dysfonctionnement pourrait être impliqué dans la physiopathologie de la mort subite et inexpliquée en épilepsie (MSIE –SUDEP en anglais). La variabilité de la fréquence cardiaque (VFC) est un outil simple et fiable pour évaluer la fonction autonomique; il est également considéré comme un prédicteur potentiel de la tachycardie ventriculaire et de la mort subite chez les patients après un infarctus du myocarde. Au cours des deux dernières décennies, la VFC a suscité beaucoup d'intérêt dans le monde de l'épilepsie. Toutefois, même si plusieurs études ont tenté d'évaluer les changements de VFC dans différentes formes d'épilepsie, les résultats ont été hétérogènes voire paradoxaux de sorte que son utilité en tant que marqueur de la MSIE est loin d’être concluant. Notons que la majorité des études ont porté sur l’épilepsie temporale. Aucune étude n’a étudié les changements de la fonction autonomique cardiaque dans l'épilepsie insulo-operculaire (EIO). Il est encore incertain si une chirurgie d’épilepsie insulaire peut accélérer la dysfonction autonomique inhérente. Dans cette étude, nous visons à étudier les changements de la VFC interictale chez les patients avec EIO. Nous avons en outre évalué l'effet de la chirurgie insulo-operculaire sur ces modifications de la VFC. Quatorze patients avec une EIO et un bon résultat post-chirurgie insulo-operculaire (Engel I-II) ont été recrutés pour cette étude. Quatorze patients appariés pour l'âge et le sexe atteints d'épilepsie du lobe temporal (ELT) et exempts de crise après une lobectomie temporale antérieure et 28 individus en bonne santé appariés selon l'âge et le sexe ont également été identifiés pour les besoins de l’étude. La VFC dans le domaine temporel RMSSD (root mean square of successive RR interval differences, pNN50 (percentage of successive RR intervals that differ by more than 50ms) et le domaine fréquentiel LF (low frequency) et HF (high frequency) ont été étudiés dans les périodes préopératoire et postopératoire (6-204 mois). La VFC avant la chirurgie des patients épileptiques fut calculée à partir des enregistrements EKG obtenus simultanément aux enregistrements vidéo-EEGs effectués dans le cadre de leur évaluation préchirurgicale. La VFC après la chirurgie fut calculée chez tous les patients et les sujets sains à partir d’un EKG de repos d'une durée d’une heure au laboratoire. Le score d’inventaire des risques de MSIE (le score SUDEP-7) a été calculé à partir des données cliniques obtenues dans le dossier médical de chaque patient. Les résultats n'ont montré aucune différence statistiquement significative dans toutes les mesures de VFC entre les groupes de patients avec EIO, de patients avec ELT avant la chirurgie et de sujets sains. Chez les patients avec EIO, le score SUDEP-7 variant de 1 à 6 (moyenne de 2,9; SD :1,2) était positivement corrélé avec le pNN50 (r = 0,671; p = 0,009 et Ln (RMSSD) (r = 0,591; p = 0,026). En postopératoire, les mesures de la VFC n'étaient pas statistiquement différentes des valeurs préopératoires ou de celles des témoins. Nous avons mené une analyse exploratoire dans laquelle nous avons stratifié les patients avec EIO en deux sous-groupes : un premier groupe (1a) dont les valeurs préopératoires de Ln (RMSSD) étaient inférieures à 3,52 (valeur moyenne de notre échantillon sain) et un second groupe (1b) dont les valeurs préopératoires étaient au-dessus. En préopératoire, dans le groupe 1a, toutes les valeurs du domaine temporel et fréquentiel (LnRMSSD, pNN50, LnLF et LnHF) étaient significativement inférieures à celles du groupe témoin (p <0,01), tandis que dans le groupe 1b, seules les valeurs du domaine temporel (LnRMSSD et pNN50) étaient significativement plus élevées que ceux du groupe témoin (p <0,01). Dans les deux groupes, les valeurs de la VFC avaient tendance à se normaliser après l'opération. En revanche, la lobectomie temporale antérieure des patients avec ELT n'a pas modifié les valeurs de HRV. Ces résultats préliminaires suggèrent que dans les EIO réfractaires, la VFC peut être soit diminuée au niveau du tonus sympathique et parasympathique, soit augmentée au niveau du tonus parasympathique. L'augmentation du tonus parasympathique est possiblement inquiétante puisqu’elle était corrélée positivement avec le score SUDEP-7. Une operculo-insulectomie n'a pas affecté négativement la VFC; au contraire, une chirurgie réussie semble entraîner une certaine ‘normalisation’ de l’HRV. Une confirmation avec un échantillon plus grand est nécessaire.Cumulative evidence supports the role of the insula in cardiac autonomic regulation whose dysfunction may be involved in the pathophysiology of sudden unexpected death in epilepsy (SUDEP). Heart rate variability (HRV) is a simple and reliable tool to assess autonomic function; it is even considered a potential predictor of ventricular tachycardia and sudden death in patients after myocardial infarction. Over the last two decades, heart rate variability (HRV) has also received much interest in epilepsy research. Several studies have tried to assess HRV changes in different epilepsy types but the results have been heterogeneous and sometimes contradictory; its role as a marker of SUDEP remains uncertain. Of note, most studies involved TLE patients and TLE surgeries; none have looked at HRV changes in insulo-opercular epilepsy (IOE) and how insular resection can affect autonomic function. In this study, we aimed to investigate changes in interictal HRV in IOE. We further evaluated the effect of insulo-opercular surgery on these HRV changes. Fourteen IOE patients who had a good outcome (Engel I-II) after an insulo-opercular surgery were enrolled in this study. Fourteen age- and sex-matched patients with temporal lobe epilepsy (TLE) who were seizure-free after temporal lobectomy and 28 age- and sex-matched healthy individuals were also included. HRV measurements including time domain root mean square of successive RR interval differences (RMSSD) and percentage of successive RR intervals that differ by more than 50ms (pNN50) and frequency domain low-frequency (LF) and high-frequency (HF) parameters were carried out in pre- and post-operative periods (6-204 months). Presurgical HRV values for epileptic patients were calculated using EKG obtained simultaneously with video-EEG recordings during the presurgical evaluation. HRV of healthy individuals and post-surgical HRV from all operated epileptic patients were calculated from a 1-hour resting electrocardiogram at the laboratory. We also collected the patients’ presurgical data to calculate the SUDEP-7 risk inventory score. Findings showed no statistically significant differences in all HRV measurements between groups of IOE patients, TLE patients before the surgery, and healthy controls. In IOE patients, the SUDEP-7 score ranged from 1 to 6 (mean 2,9; SD: 1,6) and was positively correlated with pNN50 (r=0,671; p<0,009) and LnRMSSD (r=0,591; p<0,026). Postoperatively, HRV measurements were not statistically different from either preoperative values or those of controls. We conducted exploratory analyses where we stratified IOE patients into those whose preoperative LnRMSSD values were below (Group 1a) versus above (Group 1b) a cut-off threshold of 3,52 (mean value of our healthy sample). Preoperatively, in Group 1a, all time and frequency domain values (LnRMSSD, pNN50, LnLF, and LnHF) were significantly lower than those of controls (p<0,01) while in Group 1b, only time-domain values (LnRMSSD and pNN50) were significantly higher than those of control subjects (p<0,01). In both groups, HRV values tended to normalize postoperatively. In contrast, anterior temporal lobectomy for TLE patients did not alter HRV values. Our preliminary results suggest that in refractory IOE, HRV may be either decreased globally in sympathetic and parasympathetic tones or increased in parasympathetic tone. The increase in parasympathetic tone observed preoperatively may be of clinical concern as it was positively correlated with the SUDEP-7 score. The insulo-opercular resection did not affect the HRV; successful surgery might even have a good impact on HRV changes. Confirmation with a larger sample size is necessary