Varaston turvallisuussuunnitelma

Opinnäytetyössä tehtiin varaston turvallisuussuunnitelma. Suunnitelmassa perehdyttiin siihen, mitä nykyisten kulunvalvontajärjestelmien puitteissa on mahdollista toteuttaa. Opinnäytetyössä selviää, mitä edellytetään turvalliselta varastolta ja kerrotaan kuinka turvallisuusprojekti voitaisiin toteuttaa. Kulunvalvontajärjestelmät ovat nopeasti yleistymässä, ja varastoihin räätälöityjä ohjeistuksia ei ole vielä juurikaan käsitelty. Perehdyimme opinnäytetyön aikana standardeihin, kulunvalvonta- ja rikosilmoitinjärjestelmiin, videovalvontaan ja hälytys- ja turvajärjestelmiin. Tämän opinnäytetyön teoriaosuuden ja oman pohdinnan yhteenvetona syntyi projektisuunnitelma. Suunnitelma on tarkoitettu logistiikkayrityksille, jotka ovat hankkimassa laajempaa turvallisuusjärjestelmää. Työssä käydään läpi vaihe vaiheelta asiat, jotka tulee ottaa huomioon projektin aikana.The aim of this thesis was to make a warehouse security plan. During the process it was discussed what can be done about the current access control systems. In this thesis the requirements of secure warehouse and how the security project could be done were clarified. Access control systems are becoming more and more common, but there are not so many tailored guidelines for warehouses. In this thesis the standards, access control, intrusion detection systems, video surveillance, alarm systems and security systems were researched. As a result of this thesis’s, a project plan that is based on theory and the authors’ own reasoning was made. The plan is made for logistics companies that are going to purchase a more extensive security system. The issues that need to be taken into consideration are presented step by step in this thesis

Varaston turvallisuussuunnitelma

Opinnäytetyössä tehtiin varaston turvallisuussuunnitelma. Suunnitelmassa perehdyttiin siihen, mitä nykyisten kulunvalvontajärjestelmien puitteissa on mahdollista toteuttaa. Opinnäytetyössä selviää, mitä edellytetään turvalliselta varastolta ja kerrotaan kuinka turvallisuusprojekti voitaisiin toteuttaa. Kulunvalvontajärjestelmät ovat nopeasti yleistymässä, ja varastoihin räätälöityjä ohjeistuksia ei ole vielä juurikaan käsitelty. Perehdyimme opinnäytetyön aikana standardeihin, kulunvalvonta- ja rikosilmoitinjärjestelmiin, videovalvontaan ja hälytys- ja turvajärjestelmiin. Tämän opinnäytetyön teoriaosuuden ja oman pohdinnan yhteenvetona syntyi projektisuunnitelma. Suunnitelma on tarkoitettu logistiikkayrityksille, jotka ovat hankkimassa laajempaa turvallisuusjärjestelmää. Työssä käydään läpi vaihe vaiheelta asiat, jotka tulee ottaa huomioon projektin aikana.The aim of this thesis was to make a warehouse security plan. During the process it was discussed what can be done about the current access control systems. In this thesis the requirements of secure warehouse and how the security project could be done were clarified. Access control systems are becoming more and more common, but there are not so many tailored guidelines for warehouses. In this thesis the standards, access control, intrusion detection systems, video surveillance, alarm systems and security systems were researched. As a result of this thesis’s, a project plan that is based on theory and the authors’ own reasoning was made. The plan is made for logistics companies that are going to purchase a more extensive security system. The issues that need to be taken into consideration are presented step by step in this thesis

Prognostic Value of Immune Environment Analysis in Small Bowel Adenocarcinomas with Verified Mutational Landscape and Predisposing Conditions

Background: Small bowel adenocarcinoma (SBA) is a rare yet insidious cancer with poor survival. The abundance of tumour-infiltrating lymphocytes is associated with improved survival, but the role of the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) pathway in tumour escape is controversial. We evaluated immune cell infiltration, PD1/PD-L1 expression and their prognostic value in a series of SBAs with previously verified predisposing conditions and exome-wide somatic mutation characterization. Methods: Formalin-fixed paraffin-embedded tissue sections stained for CD3, CD8, PD-L1 and PD-1 were analysed from 94 SBAs. An immune cell score (ICS) was formed from the amount of the CD3 and CD8 positive lymphocytes from the tumour centre and invasive margin. The PD-L1 and PD-1 positive immune cells (ICs) and ICS were combined into a variable called Immunoprofile. Results: High ICS, PD-L1IC and PD-1, individually and combined as Immunoprofile, were prognostic for better patient outcome. Sixty-five (69%) SBAs expressed ≥1% positive PD-L1IC. A high tumour mutation burden was common (19%) and associated with immune markers. Immunoprofile, adjusted for TNM stage, mismatch repair status, tumour location, sex and age were independent prognostic markers for disease-specific and overall survival. Conclusions: Analysing tumoral immune contexture provides prognostic information in SBA. Combining ICS, PD-1 and PD-L1IC as Immunoprofile enhanced the prognostic performance

Exome and immune cell score analyses reveal great variation within synchronous primary colorectal cancers

BACKGROUND: Approximately 4% of colorectal cancer (CRC) patients have at least two simultaneous cancers in the colon. Due to the shared environment, these synchronous CRCs (SCRCs) provide a unique setting to study colorectal carcinogenesis. Understanding whether these tumours are genetically similar or distinct is essential when designing therapeutic approaches. METHODS: We performed exome sequencing of 47 primary cancers and corresponding normal samples from 23 patients. Additionally, we carried out a comprehensive mutational signature analysis to assess whether tumours had undergone similar mutational processes and the first immune cell score analysis (IS) of SCRC to analyse the interplay between immune cell invasion and mutation profile in both lesions of an individual. RESULTS: The tumour pairs shared only few mutations, favouring different mutations in known CRC genes and signalling pathways and displayed variation in their signature content. Two tumour pairs had discordant mismatch repair statuses. In majority of the pairs, IS varied between primaries. Differences were not explained by any clinicopathological variable or mutation burden. CONCLUSIONS: The study shows major diversity within SCRCs. Rather than rely on data from one tumour, our study highlights the need to evaluate both tumours of a synchronous pair for optimised targeted therapy.Peer reviewe

Nationwide Registry-Based Analysis of Cancer Clustering Detects Strong Familial Occurrence of Kaposi Sarcoma

Many cancer predisposition syndromes are rare or have incomplete penetrance, and traditional epidemiological tools are not well suited for their detection. Here we have used an approach that employs the entire population based data in the Finnish Cancer Registry (FCR) for analyzing familial aggregation of all types of cancer, in order to find evidence for previously unrecognized cancer susceptibility conditions. We performed a systematic clustering of 878,593 patients in FCR based on family name at birth, municipality of birth, and tumor type, diagnosed between years 1952 and 2011. We also estimated the familial occurrence of the tumor types using cluster score that reflects the proportion of patients belonging to the most significant clusters compared to all patients in Finland. The clustering effort identified 25,910 birth name-municipality based clusters representing 183 different tumor types characterized by topography and morphology. We produced information about familial occurrence of hundreds of tumor types, and many of the tumor types with high cluster score represented known cancer syndromes. Unexpectedly, Kaposi sarcoma (KS) also produced a very high score (cluster score 1.91, p-value <0.0001). We verified from population records that many of the KS patients forming the clusters were indeed close relatives, and identified one family with five affected individuals in two generations and several families with two first degree relatives. Our approach is unique in enabling systematic examination of a national epidemiological database to derive evidence of aberrant familial aggregation of all tumor types, both common and rare. It allowed effortless identification of families displaying features of both known as well as potentially novel cancer predisposition conditions, including striking familial aggregation of KS. Further work with high-throughput methods should elucidate the molecular basis of the potentially novel predisposition conditions found in this study.Peer reviewe

Genetic and Epigenetic Characteristics of Inflammatory Bowel Disease–Associated Colorectal Cancer

doi: 10.1053/j.gastro.2021.04.042Background & Aims Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder associated with an elevated risk of colorectal cancer (CRC). IBD-associated CRC (IBD-CRC) may represent a distinct pathway of tumorigenesis compared to sporadic CRC (sCRC). Our aim was to comprehensively characterize IBD-associated tumorigenesis integrating multiple high-throughput approaches, and to compare the results with in-house data sets from sCRCs. Methods Whole-genome sequencing, single nucleotide polymorphism arrays, RNA sequencing, genome-wide methylation analysis, and immunohistochemistry were performed using fresh-frozen and formalin-fixed tissue samples of tumor and corresponding normal tissues from 31 patients with IBD-CRC. Results Transcriptome-based tumor subtyping revealed the complete absence of canonical epithelial tumor subtype associated with WNT signaling in IBD-CRCs, dominated instead by mesenchymal stroma-rich subtype. Negative WNT regulators AXIN2 and RNF43 were strongly down-regulated in IBD-CRCs and chromosomal gains at HNF4A, a negative regulator of WNT-induced epithelial–mesenchymal transition (EMT), were less frequent compared to sCRCs. Enrichment of hypomethylation at HNF4α binding sites was detected solely in sCRC genomes. PIGR and OSMR involved in mucosal immunity were dysregulated via epigenetic modifications in IBD-CRCs. Genome-wide analysis showed significant enrichment of noncoding mutations to 5′untranslated region of TP53 in IBD-CRCs. As reported previously, somatic mutations in APC and KRAS were less frequent in IBD-CRCs compared to sCRCs. Conclusions Distinct mechanisms of WNT pathway dysregulation skew IBD-CRCs toward mesenchymal tumor subtype, which may affect prognosis and treatment options. Increased OSMR signaling may favor the establishment of mesenchymal tumors in patients with IBD.BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder associated with an elevated risk of colorectal cancer (CRC). IBD-associated CRC (IBD-CRC) may represent a distinct pathway of tumorigenesis compared to sporadic CRC (sCRC). Our aim was to comprehensively characterize IBD-associated tumorigenesis integrating multiple high-throughput approaches, and to compare the results with in-house data sets from sCRCs. METHODS: Whole-genome sequencing, single nucleotide polymorphism arrays, RNA sequencing, genome-wide methylation analysis, and immunohistochemistry were performed using fresh-frozen and formalin-fixed tissue samples of tumor and corresponding normal tissues from 31 patients with IBD-CRC. RESULTS: Transcriptome-based tumor subtyping revealed the complete absence of canonical epithelial tumor subtype associated with WNT signaling in IBD-CRCs, dominated instead by mesenchymal stroma-rich subtype. Negative WNT regulators AXIN2 and RNF43 were strongly down-regulated in IBD-CRCs and chromosomal gains at HNF4A, a negative regulator of WNTinduced epithelial-mesenchymal transition (EMT), were less frequent compared to sCRCs. Enrichment of hypomethylation at HNF4 alpha binding sites was detected solely in sCRC genomes. PIGR and OSMR involved in mucosal immunity were dysregulated via epigenetic modifications in IBD-CRCs. Genome-wide analysis showed significant enrichment of noncoding mutations to 50 untranslated region of TP53 in IBD-CRCs. As reported previously, somatic mutations in APC and KRAS were less frequent in IBD-CRCs compared to sCRCs. CONCLUSIONS: Distinct mechanisms of WNT pathway dysregulation skew IBD-CRCs toward mesenchymal tumor subtype, which may affect prognosis and treatment options. Increased OSMR signaling may favor the establishment of mesenchymal tumors in patients with IBD.Peer reviewe

Retrotransposon insertions can initiate colorectal cancer and are associated with poor survival

Genomic instability pathways in colorectal cancer (CRC) have been extensively studied, but the role of retrotransposition in colorectal carcinogenesis remains poorly understood. Although retrotransposons are usually repressed, they become active in several human cancers, in particular those of the gastrointestinal tract. Here we characterize retro-transposon insertions in 202 colorectal tumor whole genomes and investigate their associations with molecular and clinical characteristics. We find highly variable retrotransposon activity among tumors and identify recurrent insertions in 15 known cancer genes. In approximately 1% of the cases we identify insertions in APC, likely to be tumor-initiating events. Insertions are positively associated with the CpG island methylator phenotype and the genomic fraction of allelic imbalance. Clinically, high number of insertions is independently associated with poor disease-specific survival.Peer reviewe

Syntes och uppskalning av arylsulfonylpropennitriler

The aim of this thesis was to develop a laboratory-scale process of synthesizing arylsulfonylpropenenitriles that would be transferrable to plant-scale without the need of major modifications to the process. Arylsulfonylpropenenitriles have been found to act as NF-kappaB inhibitors capable of inducing apoptosis to colon cancer cells. In addition to this they may act as irreversible protein tyrosine phosphatase inhibitors, these being related to several human diseases. Interest in their synthesis is due to their property of acting as versatile Michael-acceptors and a variety of cycloaddition reactions they may undergo. Moderately little research of their synthesis has been published. Existing methods using inexpensive substrates generally afford low yields in addition to the reactions being carried out in solvents unfit for current industrial use. Higher yields have been obtained with reagents that are either too expensive for bulk production or synthetic routes that incorporate too many reaction steps. The literature study intends to present the majority of the existing synthetic routes in addition to certain routes of structurally analogous non-nitrile vinyl sulfones. Optimization of different process parameters was carried out in this thesis in order to determine the optimal process conditions for industrial manufacture of arylsulfonylpropenenitriles. Parameters screened, such as reaction solvent, temperature, concentration, and moisture sensitivity are commonly tunable in industrial manufacture. Furthermore, crude impurity profiling was carried out in order to identify the sources of major impurities and insight on how to marginalize them. A process following modern green chemistry guidelines has been developed to synthesize a selected model target. The process consists of three reactions two of which were already well established. The main investigated reaction was determined to propagate by a radical pathway allowing rate acceleration by photocatalytic means. The process is remarkable due to no addition requirement of a photocatalyst or a photosensitizer.Syftet med detta examensarbete var att utveckla en process i laboratorieskala för syntes av aryl-sulfonylpropennitriler så att syntesen kan överföras till produktion i fabrikskala utan stora processändringar. Det har visats att arylsulfonylpropennitriler kan fungera som NF-kappaB inhibitorer kapabla av att framkalla celldöd i grovtarmscancerceller. De kan även fungera som irreversibla inhibitorer för proteintyrosinfosfataser, som berör flera olika människosjukdomar. Föreningarnas syntetiska intresse grundar sig på deras egenskap att fungera som Michael-acceptorer och deras olika cycloadditionsreaktioner. Relativt lite forskning omkring syntes av arylsulfonylpropennitriler har publicerats. En del av tidigare publicerade reaktioner, som utgör användning av förmånliga substrater, har i allmänhet lidit av lågt produktutbyte. De flesta synteser har även använt lösningsmedel vilka är klassificerade som odugliga till den nuvarande industrin. Högre produktutbyte har nåtts genom att använda reagenser som är för dyra eller genom processer som innefattar för många steg. Litteraturgranskningens avsikt är att presentera de flesta av dessa synteser i samband med synteser för likartade föreningar. Optimering av olika processparametrar utfördes i detta arbete med avsikt att fastställa de mest optimala processkonditionerna för industriell tillverkning av arylsulfonylpropennitriler. Parametrar som undersöktes var bl.a. reaktionslösningsmedel, temperatur, koncentration och inverkan av fukt p.g.a. att de kan kontrolleras lätt i industriella processer. Därtill framställdes en grov föroreningsprofil för att identifiera källorna för de främsta föroreningarna. En process för att framställa en vald modellprodukt har utvecklats i följd med moderna riktlinjer för grön kemi. Processen omfattar tre reaktioner, av vilka två redan är välkända. Den främst undersökta reaktionens hastighet ökades märkbart genom fotokatalys. Processen är anmärkningsvärd p.g.a. att inga katalytföreningar eller sensibilisatorer krävs

Ihmisen tunnistaminen vedenpohjasta käyttäen kuluttajaluokan kaikuluotaimen datalla opetettuja syviä neuroverkkoja

Suomen sameisiin vesiin hukkuu ihmisiä joka vuosi. Osa uhreista olisi mahdollista pelastaa, jos heidät löydettäisiin nopeammin. Nykyisin etsintä tapahtuu käytännössä käsin pohjaa läpikäymällä. Työn aiheena oli käydä läpi nykyistä vesipelastuksen tilaa ja prosessia sekä tutkia neuroverkkoihin perustuvaa tunnistusjärjestelmää, jolla on mahdollista nopeuttaa pelastettavan löytymistä vedenpohjasta. Työssä myös käytiin läpi tarvittava datankeräys, jonka pohjalta voitiin kerätä ja kehittää kansainvälisestikin merkittävä datasetti, joka sisältää yli 300 kuvaa ihmisestä vedenpohjassa. Työn tavoitteena oli tutkia, voidaanko kuluttajaluokan viistokaikuluotaindatasta tunnistaa ihminen, ja yleistyivätkö tulokset täysin erilliseen, erilaiseen testidatasettiin. Tulosten perusteella voidaan sanoa, että kuluttajaluokan viistokaikuluotaimilla tunnistus voidaan tehdä. Ihmisen tunnistamisen tulokset saatiin yleistymään erilliseen testidatasettiin. Datasetin pienuuden takia ei voida varmistua, että malli vielä toimii kaikissa tilanteissa ja kaikilla kaikuluotaimilla