Precise and accurate measurements of strong-field photoionisation and a transferrable laser intensity calibration standard

Ionization of atoms and molecules in strong laser fields is a fundamental process in many fields of research, especially in the emerging field of attosecond science. So far, demonstrably accurate data have only been acquired for atomic hydrogen (H), a species that is accessible to few investigators. Here we present measurements of the ionization yield for argon, krypton, and xenon with percentlevel accuracy, calibrated using H, in a laser regime widely used in attosecond science. We derive a transferrable calibration standard for laser peak intensity, accurate to 1.3%, that is based on a simple reference curve. In addition, our measurements provide a much-needed benchmark for testing models of ionisation in noble-gas atoms, such as the widely employed single-active electron approximation.Comment: Article: 5 pages, 2 figures, submitted to PRL (manuscript number LZ14457). Supplementary information: 7 pages, 6 figures, appended to end of main Articl

T cell receptor reversed polarity recognition of a self-antigen major histocompatibility complex

Central to adaptive immunity is the interaction between the αβ T cell receptor (TCR) and peptide presented by the major histocompatibility complex (MHC) molecule. Presumably reflecting TCR-MHC bias and T cell signaling constraints, the TCR universally adopts a canonical polarity atop the MHC. We report the structures of two TCRs, derived from human induced T regulatory (iTreg) cells, complexed to an MHC class II molecule presenting a proinsulin-derived peptide. The ternary complexes revealed a 180° polarity reversal compared to all other TCR-peptide-MHC complex structures. Namely, the iTreg TCR α-chain and β-chain are overlaid with the α-chain and β-chain of MHC class II, respectively. Nevertheless, this TCR interaction elicited a peptide-reactive, MHC-restricted T cell signal. Thus TCRs are not 'hardwired' to interact with MHC molecules in a stereotypic manner to elicit a T cell signal, a finding that fundamentally challenges our understanding of TCR recognition

Effect of Mavuno Phosphorus-Based Fertilizer and Manure Application on Maize Grain and Stover Yields in Western Kenya

Low crop productivity in western Kenya can be attributed to low soil fertility and limited use of organic and inorganic fertilizers. This is attributed to high costs of fertilizer, inconsistent application and duration of use. Efforts to improve and maintain soil productivity through use of manure and fertilizer among others has been ongoing in western Kenya for years. Despite these efforts low crop yield associated with limited use of common compound fertilizers is still prevalent. Remarkable increases in yield have been noted with compound fertilizers which offer additional benefits in terms of nutrient supply. Mavuno a locally blended fertilizer promoted in western Kenya offers such benefits. The objective of this study was to evaluate the effect of mavuno phosphorus-based fertilizer and manure on maize and stover yields in Nyalgunga, Nyabeda and Emusutwi sub-locations, western Kenya; where low soil fertility, coupled particularly with low available phosphorus  has been pointed out as the major factor limiting crop productivity.  The study was carried out on fields where mavuno fertilizer at 20kg P ha-1 and manure at 2t ha-1 has been applied for six years. A randomized block design was used and maize grain and stover yields calculated from the four treatment fields; control (no input), manure (2t ha-1), mavuno (20kg P ha-1) and manure (2t ha-1) + mavuno (20kg P ha-1). There was a remarkable increase in maize grain yield (control 904 kg ha -1, manure+ mavuno 2238 kg ha -1) a 148% increase in yield above control plot (p=<0.001) and stover yield (control 825 kg ha -1, manure+mavuno 1381 kg ha -1) a 67% increase above control plot (p=<0.001).  Mavuno phosphorus-based fertilizer and manure have a positive effect on maize grain and stover yield and can sustain soil productivity under long term use, their application in soils  improves availability of phosphorus to plants resulting in high yields and improved soil properties. Understanding the effect of continuous application of phosphorus-based fertilizers and manure is essential for sustaining soil productivity among small holder farms of western Kenya to meet the high food demand, which is currently forcing farmers to continuously grow maize on the same piece of land resulting to soil degradation. Keywords: Mavuno, manure, Maize grain yield, Maize stover and Western Keny

Consumer Complaints and Company Market Value

Consumer complaints affect company market value and common sense suggests that a negative impact is expected. However, do complaints always negatively impact company market value? We hypothesize in this study that complaints may have a non-linear effect on market value. Positive (e.g. avoiding high costs to solve complaints) and negative (e.g. speedy and intense diffusion) tradeoffs may occur given the level of complaints. To test our non-linear hypothesis, a panel data was collected from cell phone service providers from 2005 to 2013. The results supported our tradeoff rationale. Low levels of complaints allow for companies to increase market value, while high levels of complaints cause increasing harm to market value. The sample, model and period considered in this study, indicates a level of 0.49 complaints per thousand consumers as the threshold for a shift in tradeoffs. The effects on market value become increasingly negative when trying to make reductions to move below this level, due to negative tradeoffs

Survival Analysis of Cancer Patients in North Eastern Nigeria from 2004 – 2017 – A Kaplan - Meier Method

BACKGROUND: Cancer is a deadly malignant disease and is prevalent in Sub Saharan Africa. The North East part of Nigeria in particular and the country, in general, are struggling to cope with the increasing burden of cancer and other communicable and non-communicable diseases. The situation is worsened by the ongoing insurgency and terrorist activities in the area. AIM: The aim of this paper is to present the research findings from a cohort study aimed at the analysis of the estimation of the survivorship time of the real data of cancer patients in the North-eastern part of Nigeria and to establish if the insurgency in the region has contributed negatively to the life expectancy of its inhabitants. MATERIAL AND METHODS: The record of 1,090 patients from medical records departments of the University of Maiduguri Teaching Hospital (UMTH), located in Maiduguri, the capital city of Borno State in northeast Nigeria was obtained. The record showed patients that were diagnosed and died of one type of cancer or the other from 2004 to 2017. All the cancer cases included in the present study were grouped into sex, age, marital status, occupation, date admitted and date of death/discharge. Descriptive statistics and Kaplan-Meier method were used to analyse the data using SPSS version 23 while Microsoft EXCEL and Minitab 16.0 were used for data cleansing and organisation. RESULTS: Of the 1,090 patients analysed, 920 (84.40%) experienced the event, i.e. death, while 170 (15.60%) patients were censored. The data were analysed based on the ages and sex of the patients. 50.20% of the patients were of ages 21-50 years. The proportions of patients in this age bracket surviving past 7 days are 75%, while those between ages 80 years and above is 12 days. Others are of survival time of 5 days (ages 0-20 years) and 7 days (51-79 years). Using sex, 75% of the patients’ survival time is 7 days in the case of male and 6 days for females. It is safe to say that the survival time for cancer patients of the university the Maiduguri is 6 days and the result reflects the Northeastern part of Nigeria. This is because the hospital is one of few tertiary healthcare facilities in that area and consequently, cancer cases are often referred there. CONCLUSION: Cancer incidence is high, and the probability of survival reduces as the survival time increases. This is a dire situation in need of urgent intervention from the government, groups and individuals to tackle the scourge of cancer, thereby improving on the life expectancy battered by the ongoing Boko Haram insurgency in that region

Performance of Different Diagnostic PD-L1 Clones in Head and Neck Squamous Cell Carcinoma

Background: The approval of immune checkpoint inhibitors in combination with specific diagnostic biomarkers presents new challenges to pathologists as tumor tissue needs to be tested for expression of programmed death-ligand 1 (PD-L1) for a variety of indications. As there is currently no requirement to use companion diagnostic assays for PD-L1 testing in Germany different clones are used in daily routine. While the correlation of staining results has been tested in various entities, there is no data for head and neck squamous cell carcinomas (HNSCC) so far. Methods: We tested five different PD-L1 clones (SP263, SP142, E1L3N, 22-8, 22C3) on primary HNSCC tumor tissue of 75 patients in the form of tissue microarrays. Stainings of both immune and tumor cells were then assessed and quantified by pathologists to simulate real-world routine diagnostics. The results were analyzed descriptively and the resulting staining pattern across patients was further investigated by principal component analysis and non-negative matrix factorization clustering. Results: Percentages of positive immune and tumor cells varied greatly. Both the resulting combined positive score as well as the eligibility for certain checkpoint inhibitor regimens was therefore strongly dependent on the choice of the antibody. No relevant co-clustering and low similarity of relative staining patterns across patients was found for the different antibodies. Conclusions: Performance of different diagnostic anti PD-L1 antibody clones in HNSCC is less robust and interchangeable compared to reported data from other tumor entities. Determination of PD-L1 expression is critical for therapeutic decision making and may be aided by back-to-back testing of different PD-L1 clones

Discovery of a selective islet peptidome presented by the highest-risk HLA-DQ8trans molecule

HLA-DQ2/8 heterozygous individuals are at far greater risk for type 1 diabetes (T1D) development by expressing HLA-DQ8trans on antigen-presenting cells compared with HLA-DQ2 or -DQ8 homozygous individuals. Dendritic cells (DC) initiate and shape adaptive immune responses by presenting HLA-epitope complexes to naïve T cells. To dissect the role of HLA-DQ8trans in presenting natural islet epitopes, we analyzed the islet peptidome of HLA-DQ2, -DQ8, and -DQ2/8 by pulsing DC with pre-proinsulin (PPI), IA-2, and GAD65. Quality and quantity of islet epitopes presented by HLA-DQ2/8 differed from -DQ2 or -DQ8. We identified two PPI epitopes solely processed and presented by HLA-DQ2/8 DC: an HLA-DQ8trans-binding signal-sequence epitope previously identified as CD8 T-cell epitope and a second epitope that we previously identified as CD4 T-cell epitope with increased binding to HLA-DQ8trans upon posttranslational modification. IA-2 epitopes retrieved from HLA-DQ2/8 and -DQ8 DC bound to HLA-DQ8cis/trans. No GAD65 epitopes were eluted from HLA-DQ. T-cell responses were detected against the novel islet epitopes in blood from patients with T1D but scantly detected in healthy donor subjects. We report the first PPI and IA-2 natural epitopes presented by highest-risk HLA-DQ8trans. The selective processing and presentation of HLA-DQ8trans-binding islet epitopes provides insight in the mechanism of excessive genetic risk imposed by HLA-DQ2/8 heterozygosity and may assist immune monitoring of disease progression and therapeutic intervention as well as provide therapeutic targets for immunotherapy in subjects at risk for T1D.</p

Conservative Therapy is an Effective Option in Patients With Localized Infection After Penile Implant Surgery

INTRODUCTION: Traditionally, penile implant (PI) infections have been managed by removal with immediate or delayed replacement. Recently, interest has been focused on conservative therapy (CT) using antibiotic therapy. AIM: To investigate the success rate and predictive factors affecting the outcome of CT in PI infection patients. METHODS: Patients diagnosed with early, localized PI infection were considered candidates for CT. Exclusion criteria included temperature >37.5°C, WBC >13,000/μL, and appearance of any sign of sepsis. In patients with purulent drainage, culture swabs were taken and an antibiotic was chosen based on sensitivity results. Oral antibiotics were used until the local infection was completely resolved. Patients were evaluated weekly during this process. RESULTS: Thirty-seven patients were retrospectively reviewed and constituted the study population. Mean age was 58.1 (range 37-85; SD 9.9) years. All were diabetic. Mean BMI was 31.8 (range 24-47; SD 5.0). PI was malleable in 33 cases and inflatable in 4 cases. Culture results (n = 19) included Staphylococcus epidermidis (42 %), pseudomonas (21%), Escherichia coli (21%), and S aureus (16%). Four of 37 patients needed the PI removed due to CT failure and onset of systemic symptoms, at a mean time-point of 75 ± 1.8 days after CT commencement. In men who were cured, mean time to complete healing was 49 (range 29-97; SD 15.8) days. Two of 37 patients (5%) had PI removal because of persistent penile pain despite complete wound healing, at a mean time point of 128 ± 2.5 days after CT commencement. All men managed conservatively resumed sexual intercourse. CONCLUSION: CT of localized PI infection appears to be a viable option for such patients, with the majority of patients retaining their implant and resuming sexual activity