Supersymmetric 4D Orientifolds of Type IIA with D6-branes at Angles

We study a certain class of four-dimensional N=1 supersymmetric orientifolds for which the world-sheet parity transformation is combined with a complex conjugation in the compact directions. We investigate in detail the orientifolds of the Z_3, Z_4, Z_6 and Z_6' toroidal orbifolds finding solutions to the tadpole cancellation conditions for all models. Generically, all the massless spectra turn out to be non-chiral.Comment: 28 pages, LaTeX, 6 figures; v2: slight modification of closed string spectr

N=1 and non-supersymmetric open string theories in six and four space-time dimensions

This thesis contains an introductory chapter on orbifolds. The following chapter explains the foundations of orientifolds. Chapters 4-7 present own research. In chapter 4 we quantize open strings with linear boundary conditions, as they show up in electro-magnetic fields. We quantize the zero-modes for toroidal compactifications, too. As an application we calculate the commutator of the coordinate fields in the case of general constant Neveu-Schwarz U(1)-field strengths. Thereby we confirm previous results on non-commutativity of open string theories in Neveu-Schwarz backgrounds. Chapter 5 reviews the results of a former publication [1] on asymmetric orientifolds, supplemented by some recent insights in connection with chapter 4. Chapter 6 summarizes publication [2] where we investigated to what extend one can build phenomenologically interesting models from toroidal orientifolds. By turning on magnetic fluxes on D9-branes we induce chiral fermions. Most calculations are performed in an (equivalent) T-dual picture. Here the number of chiral fermions is given by the topological intersection number of D-branes. In orientifolds of toroidal compactifications one obtains either non-chiral or non-supersymmetric orientifold solutions. However both properties can be reconciled in orientifolds that are obtained from specific supersymmetric orbifold compactifications. In chapter 7 we present the ``sigma Omega'' -Orientifold on a T^6/Z(4) orbifold. As a very attractive example we investigate a supersymmetric U(4) x U(2)^3_L x U(2)^3_R model that is broken to an MSSM-like model by switching on suitable background fields in the LEEA. This chapter is based on our publication [3]. An appendix is supplemented with formulas applied in the text, as well as proofs to two theorems.Comment: PhD-Thesis; LaTeX, 242 pages, 43 figures, gzipped ps-file has < 5 MB; pdf-file has < 3 MB,references and remarks concerning historical development of the subject adde

Noncommutative Compactifications of Type I Strings on Tori with Magnetic Background Flux

We construct six- and four-dimensional toroidal compactifications of the Type I string with magnetic flux on the D-branes. The open strings in this background probe a noncommutative internal geometry. Phenomenologically appealing features such as chiral fermions and supersymmetry breaking in the gauge sector are naturally realized by these vacua. We investigate the spectra of such noncommutative string compactifications and in a bottom-up approach discuss the possibility to obtain the standard or some GUT like model.Comment: TeX harvmac, 25 pages, 5 figure

Measuring Endogenous Corticosterone in Laboratory Mice - a Mapping Review, Meta-Analysis, and Open Source Database

Evaluating stress in laboratory animals is a key principle in animal welfare. Measuring corticosterone is a common method to assess stress in laboratory mice. There are, however, numerous methods to measure glucocorticoids with differences in sample matrix (e.g., plasma, urine) and quantification techniques (e.g., enzyme immunoassay or radioimmunoassay). Here, the authors present a mapping review and a searchable database, giving a complete overview of all studies measuring endogenous corticosterone in mice up to February 2018. For each study, information was recorded regarding mouse strain and sex; corticosterone sample matrix and quantification technique; and whether the study covered the research theme animal welfare, neuroscience, stress, inflammation, or pain (the themes of specific interest in our consortium). Using all database entries for the year 2012, an exploratory meta-regression was performed to determine the effect of predictors on basal corticosterone concentrations. Seventy-five studies were included using the predictors sex, time-since-lights-on, sample matrix, quantification technique, age of the mice, and type of control. Sex, time-since-lights-on, and type of control significantly affected basal corticosterone concentrations. The resulting database can be used, inter alia, for preventing unnecessary duplication of experiments, identifying knowledge gaps, and standardizing or heterogenizing methodologies. These results will help plan more efficient and valid experiments in the future and can answer new questions in silico using meta-analyses

Gaugino Condensation and Nonperturbative Superpotentials in Flux Compactifications

There are two known sources of nonperturbative superpotentials for K\"ahler moduli in type IIB orientifolds, or F-theory compactifications on Calabi-Yau fourfolds, with flux: Euclidean brane instantons and low-energy dynamics in D7 brane gauge theories. The first class of effects, Euclidean D3 branes which lift in M-theory to M5 branes wrapping divisors of arithmetic genus 1 in the fourfold, is relatively well understood. The second class has been less explored. In this paper, we consider the explicit example of F-theory on $K3 \times K3$ with flux. The fluxes lift the D7 brane matter fields, and stabilize stacks of D7 branes at loci of enhanced gauge symmetry. The resulting theories exhibit gaugino condensation, and generate a nonperturbative superpotential for K\"ahler moduli. We describe how the relevant geometries in general contain cycles of arithmetic genus $\chi \geq 1$ (and how $\chi > 1$ divisors can contribute to the superpotential, in the presence of flux). This second class of effects is likely to be important in finding even larger classes of models where the KKLT mechanism of moduli stabilization can be realized. We also address various claims about the situation for IIB models with a single K\"ahler modulus.Comment: 24 pages, harvmac, no figures, references adde

Tumor infiltrating T cells influence prognosis in stage I-III non-small cell lung cancer

Background: T cell infiltration in non-small cell lung cancer (NSCLC) is essential for the immunological response to malignant tissue, especially in the era of immune-checkpoint inhibition. To investigate the prognostic impact of CD4(+) T helper cells (T-h), CD8(+) cytotoxic (T-c) and FOXP3(+) regulatory T (T-reg) cells in NSCLC, we performed this analysis. Methods: By counterstaining of CD4, CD8 and FOXP3 we used immunohistochemistry on tissue microarrays (TMA) to evaluate peritumoral T-h cells, T(reg )cells and T-c cells in n=294 NSCLC patients with pTNM stage I-III disease. Results: Strong CD4(+) infiltration was associated with higher tumor stages and lymphonodal spread. However, strong CD4(+) infiltration yielded improved overall survival (OS) (P=0.014) in adenocarcinoma (ADC) and large cell carcinoma (LCC) but not in squamous cell carcinoma (SCC). A CD4/CD8 ratio 0.05). Here, prognostic effects were prominent in PD-L1 positive SCC (P=0.023) but not in PD-L1 negative SCC (P=0.236). Conclusions: High proportion of CD8(+) T-c cells correlated with improved prognostic outcome in stage I-III NSCLC. T-h cells and T-reg cells have implications on outcome with respect to tumor histology and biology

Prognostic impact of CD34 and SMA in cancer-associated fibroblasts in stage I-III NSCLC

Background Epithelial-to-mesenchymal transition (EMT) is a crucial step in lung cancer pathogenesis. Among others, cancer-associated fibroblasts (CAFs) are reported to regulate this process. Objectives To investigate the prognostic and clinical impact, we analyzed CD34+ and SMA+ CAFs in non-small cell lung cancer (NSCLC). Methods Retrospectively, immunohistochemistry was performed to study stromal protein expression of both CD34 and SMA in 304 NSCLC patients with pTNM stage I-III disease. All tissue samples were embedded on tissue microarrays (TMAs). Results Our analysis revealed an association for CD34+ CAFs with G1/2 tumors and adenocarcinoma histology. Moreover CD34+ CAFs were identified as an independent prognostic factor (both for progression free survival [PFS] and overall survival [OS] in stage I-III NSCLC). Besides, SMA+ expression correlated with higher pTNM-tumor stages and lymphatic spread (pN stage). In turn, SMA-negativity was associated with improved PFS, but no prognostic impact was found on OS. Of interest, neither CD34+ CAFs nor SMA+ CAFs were associated with the primary tumor size, localization and depth of infiltration (pT stage). Conclusions CD34 was identified as an independent prognostic marker in pTNM stage I-III NSCLC. Moreover, loss of CD34+ CAFs might influence the dedifferentiation of the NSCLC tumor from its cell origin. Finally, SMA+ CAFs are more prevalent in NSCLC tumors of higher stages and lymphonodal positive NSCLC

Rapid point-of-care detection of SARS-CoV-2 using reverse transcription loop-mediated isothermal amplification (RT-LAMP)

BACKGROUND: Fast, reliable and easy to handle methods are required to facilitate urgently needed point-of-care testing (POCT) in the current coronavirus pandemic. Life-threatening severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread all over the world, infecting more than 33,500,000 people and killing over 1 million of them as of October 2020. Infected individuals without any symptoms might still transfer the virus to others underlining the extraordinary transmissibility of this new coronavirus. In order to identify early infections effectively, treat patients on time and control disease spreading, rapid, accurate and onsite testing methods are urgently required. RESULTS: Here we report the development of a loop-mediated isothermal amplification (LAMP) based method to detect SARS-CoV-2 genes ORF8 and N directly from pharyngeal swab samples. The established reverse transcription LAMP (RT-LAMP) assay detects SARS-CoV-2 directly from pharyngeal swab samples without previous time-consuming and laborious RNA extraction. The assay is sensitive and highly specific for SARS-CoV-2 detection, showing no cross reactivity when tested on 20 other respiratory pathogens. The assay is 12 times faster and 10 times cheaper than routine reverse transcription real-time polymerase chain reaction, depending on the assay used. CONCLUSION: The fast and easy to handle RT-LAMP assay amplifying specifically the genomic regions ORF8 and N of SARS-CoV-2 is ideally suited for POCT at e.g. railway stations, airports or hospitals. Given the current pandemic situation, rapid, cost efficient and onsite methods like the here presented RT-LAMP assay are urgently needed to contain the viral spread