Immune Infiltration and Prostate Cancer

It is becoming increasingly clear that inflammation influences prostate cancer development and that immune cells are among the primary drivers of this effect. This information has launched numerous clinical trials testing immunotherapy drugs in prostate cancer patients. The results of these studies are promising but have yet to generate a complete response. Importantly, the precise immune profile that determines clinical outcome remains unresolved. Individual immune cell types are divided into various functional subsets whose effects on tumor development may differ depending on their particular phenotype and functional status, which is often shaped by the tumor microenvironment. Thus, this review aims to examine the current knowledge regarding the role of inflammation and specific immune cell types in mediating prostate cancer progression to assist in directing and optimizing immunotherapy targets, regimens and responses and to uncover areas in which further research is needed. Finally, a summary of ongoing immunotherapy clinical trials in prostate cancer is provided

Effects of Integrating Technology on the Fitness Levels of Elementary Students

The purpose of this research was to determine the effects of using technology in physical education classes on the cardiovascular endurance of fourth grade students. Three classes of fourth grade students were randomly assigned to Heart Rate Monitor (HRM), Pedometer, or Control groups and participated in the same physical education activities for 24 weeks. Comparisons on the ½ mile fitness run of the 3 groups were not significantly different from each other (p = .3580) at the beginning of the study. There were no significant correlations (p > 0.05) between activity levels and mile run times after the 24 weeks. A two-way (Treatment x Gender) ANOVA was used to analyse mile run times after the 24 weeks. The main effect of gender (p < 0.01) was significant while the effect of treatment (p > 0.05) and the Treatment x Gender interaction (p > 0.05) were not

Tumor infiltrating B-cells are increased in prostate cancer tissue

BACKGROUND: The presence of increased B-cell tumor infiltrating lymphocytes (TILs) was seen in mouse prostate cancer (PCa) but has not been fully documented in human PCa. We, therefore, investigated the density of infiltrating B cells within human PCa utilizing a quantitative computational method. METHODS: Archived radical prostatectomy specimens from 53 patients with known clinical outcome and D’Amico risk category were obtained and immunohistochemically (IHC) stained for the B cell marker, CD20. Slides were reviewed by a genitourinary pathologist who manually delineated the tumoral regions of PCa. Slides were digitally scanned and a computer algorithm quantified the area of CD20 stained B-cells as a measure of B cell density within the outlined regions of prostate cancer (intra-tumoral region), versus extra-tumoral prostate tissue. Correlations were analyzed between B-cell density and demographic and clinical variables, including D’Amico risk groups and disease recurrence. RESULTS: For the entire cohort, the mean intra-tumoral B cell density was higher (3.22 SE = 0.29) than in the extra-tumoral region of each prostatectomy section (2.24, SE = 0.19) (paired t test; P < 0.001). When analyzed according to D’Amico risk group, the intra-tumoral B cell infiltration in low risk (0.0377 vs. 0.0246; p = 0.151) and intermediate risk (0.0260 vs. 0.0214; p = 0.579) patient prostatectomy specimens did not show significantly more B-cells within the PCa tumor. However, patient specimens from the high-risk group (0.0301 vs. 0.0197; p < 0.001) and from those who eventually had PCa recurrence or progression (0.0343 vs. 0.0246; p = 0.019) did show significantly more intra-tumoral CD20+ B-cell staining. Extent of B-cell infiltration in the prostatectomy specimens did not correlate with any other clinical parameters. CONCLUSIONS: Our study shows that higher B-cell infiltration was present within the intra-tumoral PCa regions compared to the extra-tumoral benign prostate tissue regions in prostatectomy sections. For this study we developed a new method to measure B-cells using computer-assisted digitized image analysis. Accurate, consistent quantitation of B-cells in prostatectomy specimens is essential for future clinical trials evaluating the effect of B cell ablating antibodies. The interaction of B-cells and PCa may serve as the basis for new therapeutic targets

Retroviral matrix and lipids, the intimate interaction

Retroviruses are enveloped viruses that assemble on the inner leaflet of cellular membranes. Improving biophysical techniques has recently unveiled many molecular aspects of the interaction between the retroviral structural protein Gag and the cellular membrane lipids. This interaction is driven by the N-terminal matrix domain of the protein, which probably undergoes important structural modifications during this process, and could induce membrane lipid distribution changes as well. This review aims at describing the molecular events occurring during MA-membrane interaction, and pointing out their consequences in terms of viral assembly. The striking conservation of the matrix membrane binding mode among retroviruses indicates that this particular step is most probably a relevant target for antiviral research

The molecular and cellular origin of human prostate cancer

Prostate cancer is the most commonly diagnosed male malignancy. Despite compelling epidemiology, there are no definitive aetiological clues linking development to frequency. Pre-malignancies such as proliferative inflammatory atrophy (PIA) and prostatic intraepithelial neoplasia (PIN) yield insights into the initiating events of prostate cancer, as they supply a background "field" for further transformation. An inflammatory aetiology, linked to recurrent prostatitis, and heterologous signalling from reactive stroma and infiltrating immune cells may result in cytokine addiction of cancer cells, including a tumour-initiating population also known as cancer stem cells (CSCs). In prostate tumours, the background mutational rate is rarely exceeded, but genetic change via profound sporadic chromosomal rearrangements results in copy number variations and aberrant gene expression. In cancer, dysfunctional differentiation is imposed upon the normal epithelial lineage, with disruption/disappearance of the basement membrane, loss of the contiguous basal cell layer and expansion of the luminal population. An initiating role for androgen receptor (AR) is attractive, due to the luminal phenotype of the tumours, but alternatively a pool of CSCs, which express little or no AR, has also been demonstrated. Indolent and aggressive tumours may also arise from different stem or progenitor cells. Castrate resistant prostate cancer (CRPC) remains the inevitable final stage of disease following treatment. Time-limited effectiveness of second-generation anti-androgens, and the appearance of an AR-neuroendocrine phenotype imply that metastatic disease is reliant upon the plasticity of the CSC population, and indeed CSC gene expression profiles are most closely related to those identified in CRPCs

The Cyclist\u27s safety in Slovenia

V diplomski nalogi je obravnavano stanje varnosti kolesarjev pri nas. Z večjim številom kolesarjev se bo izboljšala tudi njihova varnost, pa vendar sta največji težavi, ki zavirata še večjo uporabo koles za vsakdanje potrebe, prometna varnost in slaba kolesarska infrastruktura. Kljub temu, da so kolesarji nekako začetniki prometa, so z razvojem motornega prometa vodilno vlogo prevzeli predvsem avtomobili. Kolesarji, skupaj s pešci spadajo med najbolj ogrožene skupine prometnih udeležencev. Na začetku diplomske naloge je predstavljena zgodovina razvoja kolesa in kolesarstva, sledi pregled pravne ureditve in stanje varnosti kolesarjev. Pregled stanja varnosti nam pokaže, da se kljub večjemu številu kolesarjev njihovo število smrti v prometnih nesrečah ne povečuje, temveč je že nekaj let približno enako. Na pravnem področju je z novim zakonom že viden napredek, predvsem pa se bo potrebno še bolj približati ciljem, ki so zastavljeni v Nacionalnem programu varnosti cestnega prometa. V drugem delu diplomske naloge je večji del posvečen kolesarski infrastrukturi in njenim izboljšavam. Počasi so že vidne izboljšave na tem področju. Največ je narejenega v Ljubljani in na področju kolesarskih poti za rekreativne kolesarje. Ukrepe, kot so zmanjševanje števila vozil in povečevanje števila kolesarjev, največkrat zasledimo v urbanih središčih večjih tujih razvitih mest. Tukaj je potrebno poudariti, da gre večinoma za skandinavska, nizozemska in nemška mesta.Cyclist’s safety will improve with increasing their numbers, but two biggest problems, that are traffic safety and poor cycling infrastructure, still remain and hold back increased use of bicycles in everyday transportation. Despite the fact, that cyclists are pioneers of transportation, development of motor transportation took over their leading role. Together with pedestrians, the bicyclists are among the most vulnerable traffic participants. The thesis begins with history of bicycle and development of cycling, and follows with the review of regulations and safety of cyclists. State of safety review shows that despite growing numbers of cyclist, death casualties in traffic accidents do not increase, but stay approximately the same for several years. The progress in the regulation is already visible with the new laws, though it will be also required to pursuit the objectives from National Road Traffic Safety program. Second part of the thesis is focused on cycling infrastructure and improvements. Improvements in this field are already visible, most of them in city Ljubljana and in field of recreational cycling routes. Reducing number of vehicles and increasing numbers of cyclists are measures that can be seen in urban centers of bigger and more developed cities. It should be stated, that this applies to mostly Scandinavian, Dutch and German cities

Formative assessment of second and fifth graders in mathematics instruction

Formative assessment is an important part of school teaching, but it is often abandoned or unstructured due to time constraints. The purpose of formative assessment is to provide feedback, which can help students achieve their goals. The master's thesis presents the pre-assessment and assessment of knowledge in mathematics with an emphasis on formative assessment as a way to improve students' learning motivation and success, as well as present an opportunity to more efficiently adapt the further learning process to students. The thesis refers to the already conducted research in this field as well as to other professional literature. The empirical part is based on quantitative research, the main purpose of which was to investigate the ways, causes and frequency of formative assessment in the process of teaching mathematics to 2nd and 5th grade students. The main interest is in whether teachers in the 5th grade perform formative assessment in mathematics more often than teachers in the 2nd grade, and whether they use different methods and techniques of implementation. In addition to that, we researched how often, in what ways, and with what purpose teachers carry out formative assessment in mathematics lessons, if and how they adapt formative assessment to different classroom factors (individual characteristics of students, specifics of learning content, distance learning) and the level of competence to perform formative assessment in mathematics lessons teachers feel they have. Teachers of 2nd and 5th grades were included in the research, and the necessary data were obtained with the Enka online survey, i.e. with the survey questionnaire. The results show statistically significant differences in the frequency of formative assessment between 2nd and 5th grade teachers- 5th grade teachers perform formative assessment more often than 2nd grade teachers, but not in the methods of implementation. Teachers most often use KŽN and Semafor techniques, and they carry out formative assessment in order to determine the acquired knowledge of students. The results of the survey showed that teachers adapt the methods of formative monitoring to the individual characteristics of students, while the specifics of learning content and distance learning are mostly adjusted only with different frequency of formative assessment. Teachers acknowledge that they may not always feel competent enough to carry out formative assessment in mathematics lessons, however in most cases they do not attend any additional training on this topic. The conclusion is that the teachers do not use formally acquired knowledge when performing formative assessment, but rather implement it in their own way. It is hoped that the obtained findings will inspire teachers and other pedagogical workers to structurally start using formative assessment, through which they can adapt the pedagogical process to individual characteristics of students, the specifics of learning content and to other circumstances

Architectural design of smart street lighting

V diplomskem delu predstavljam arhitekturo predlaganega sistema pametne javne razsvetljave, ki rešuje kopico problemov, ki se pojavljajo pri obstoječih sistemih. Z implementacijo solarnega napajanja, LED svetil z možnostjo zatemnitve, senzorjev gibanja, brezžične komunikacije in pametnega nadzornega sistema se nam odpirajo vrata v boljšo prihodnost. Nižji stroški porabe energije, manj emisij ogljika in večja fleksibilnost so samo nekateri izmed razlogov, ki kažejo na ogromen napredek in ponujajo dodatne možnosti za naprej. Začenjam s kratko predstavitvijo spektra elektromagnetnega valovanja in svetlobno-tehničnih veličin. Nadaljujem z opisom različnih svetil ter poskušam razložiti, zakaj so LED žarnice prava izbira za naš sistem. Za tem se posvečam internetu stvari, ki vključuje senzorsko omrežje, brezžične tehnologije, protokole ter pametni nadzorni sistem. V naslednjem poglavju opisujem celoten predlagani sistem in njegovo arhitekturo, od strojne opreme do omrežne komunikacije, ter delovanje poskušam prikazati tudi z algoritmi. Na koncu sem izdelal še projekt, ki na minimalističen način prikaže delovanje sistema in komunikacijo med nadzornim centrom, MQTT posrednikom in LED svetilko.In this bachelor thesis, I\u27m presenting architecture of the proposed smart street lighting system, which solves a lot of problems that arise with the current systems. With the implementation of solar power, LEDs with dimming, motion sensors, wireless communication and the smart control system, the future looks bright. Lower cost of energy consumption, less carbon emissions and greater flexibility are just some of the reasons that show a tremendous amount of progress and offer further possibilities. I begin with a brief presentation of the spectrum of electromagnetic waves and technical quantities of light. I continue with the description of different types of bulbs and I try to explain why LED bulbs are the right choice for our system. Then, I focus on the Internet of things, which includes a sensor network, wireless technologies, protocols and a smart control system. In the next chapter, I describe the whole proposed system and its architecture, from hardware to network communication, and I try to show the operation with algorithms. In the end, I also created a project that, in a minimalistic way, shows the functioning of the system and communication between the control center, the MQTT broker and the LED lamp