Missing energies at pair creation

Wilson cloud chamber measurements of the separated spectra of positrons and electrons produced by gamma quanta of 6.14 MeV differ considerably from the theoretically predicted spectra by BETHE and HEITLER, but are in good agreement with those of a modified theory of pair creation

Genetic diversity of Clostridium perfringens type A isolates from animals, food poisoning outbreaks and sludge

BACKGROUND: Clostridium perfringens, a serious pathogen, causes enteric diseases in domestic animals and food poisoning in humans. The epidemiological relationship between C. perfringens isolates from the same source has previously been investigated chiefly by pulsed-field gel electrophoresis (PFGE). In this study the genetic diversity of C. perfringens isolated from various animals, from food poisoning outbreaks and from sludge was investigated. RESULTS: We used PFGE to examine the genetic diversity of 95 C. perfringens type A isolates from eight different sources. The isolates were also examined for the presence of the beta2 toxin gene (cpb2) and the enterotoxin gene (cpe). The cpb2 gene from the 28 cpb2-positive isolates was also partially sequenced (519 bp, corresponding to positions 188 to 706 in the consensus cpb2 sequence). The results of PFGE revealed a wide genetic diversity among the C. perfringens type A isolates. The genetic relatedness of the isolates ranged from 58 to 100% and 56 distinct PFGE types were identified. Almost all clusters with similar patterns comprised isolates with a known epidemiological correlation. Most of the isolates from pig, horse and sheep carried the cpb2 gene. All isolates originating from food poisoning outbreaks carried the cpe gene and three of these also carried cpb2. Two evolutionary different populations were identified by sequence analysis of the partially sequenced cpb2 genes from our study and cpb2 sequences previously deposited in GenBank. CONCLUSION: As revealed by PFGE, there was a wide genetic diversity among C. perfringens isolates from different sources. Epidemiologically related isolates showed a high genetic similarity, as expected, while isolates with no obvious epidemiological relationship expressed a lesser degree of genetic similarity. The wide diversity revealed by PFGE was not reflected in the 16S rRNA sequences, which had a considerable degree of sequence similarity. Sequence comparison of the partially sequenced cpb2 gene revealed two genetically different populations. This is to our knowledge the first study in which the genetic diversity of C. perfringens isolates both from different animals species, from food poisoning outbreaks and from sludge has been investigated

Detection and identification by PCR of Clostridium chauvoei in clinical isolates, bovine faeces and substrates from biogas plant

<p>Abstract</p> <p>Background</p> <p><it>Clostridium chauvoei </it>causes blackleg, an acute disease associated with high mortality in ruminants. The apparent primary port of entry is oral, during grazing on pasture contaminated by spores. Cases of blackleg can occur year after year on contaminated pastures. A method to determine the prevalence of <it>C. chauvoei </it>spores on pasture would be useful.</p> <p>The standard method for <it>C. chauvoei </it>detection is culture and biochemical identification, which requires a pure culture. In most muscle samples from cattle dead from blackleg the amount of <it>C. chauvoei </it>in samples is high and the bacterium can easily be cultured, although some samples may be contaminated. Detection by PCR would be faster and independent of contaminating flora.</p> <p>Digested residues from biogas plants provide an excellent fertiliser, but it is known that spore-forming baeria such as <it>Clostridium </it>spp. are not reduced by pasteurisation. The use of digested residues as fertiliser may contribute to the spread of <it>C. chauvoei</it>. Soil, manure and substrate from biogas plants are contaminated with other anaerobic bacteria which outgrow <it>C. chauvoei</it>. Therefore, detection by PCR is would be useful. This study applied a PCR-based method to detect of <it>C. chauvoei </it>in 25 muscle and blood samples, 114 manure samples, 84 soil samples and 33 samples from the biogas process.</p> <p>Methods</p> <p>Muscle tissues from suspected cases of blackleg were analysed both by the standard culture method followed by biochemical identification and by PCR, with and without preculture. To investigate whether muscle tissue samples are necessary, samples taken by swabs were also investigated. Samples from a biogas plant and manure and soil from farms were analysed by culture followed by PCR. The farms had proven cases of blackleg. For detection of <it>C. chauvoei </it>in the samples, a specific PCR primer pair complementary to the spacer region of the 16S-23S rRNA gene was used.</p> <p>Results</p> <p><it>Clostridium chauvoei </it>was detected in 32% of muscle samples analysed by culture with identification by biochemical methods and in 56% of cases by culture in combination with PCR. <it>Clostridium chauvoei </it>was detected in 3 (out of 11) samples from the biogas plants collected before pasteurisation, but samples taken after pasteurisation and after digestion all tested negative. <it>Clostridium chauvoei </it>was not detected in any soil or silage samples and only one manure samples tested positive.</p> <p>Conclusion</p> <p>The diagnostic method used for <it>C. chauvoei </it>was not applicable in estimating the risk of blackleg on particular pastures from manure or soil samples, but found to be highly useful for clinical samples.</p

Treatment with Anti-HER2 Chimeric Antigen Receptor Tumor-Infiltrating Lymphocytes (CAR-TILs) Is Safe and Associated with Antitumor Efficacy in Mice and Companion Dogs

Patients with metastatic melanoma have a historically poor prognosis, but recent advances in treatment options, including targeted therapy and immunotherapy, have drastically improved the outcomes for some of these patients. However, not all patients respond to available treatments, and around 50% of patients with metastatic cutaneous melanoma and almost all patients with metastases of uveal melanoma die of their disease. Thus, there is a need for novel treatment strategies for patients with melanoma that do not benefit from the available therapies. Chimeric antigen receptor-expressing T (CAR-T) cells are largely unexplored in melanoma. Traditionally, CAR-T cells have been produced by transducing blood-derived T cells with a virus expressing CAR. However, tumor-infiltrating lymphocytes (TILs) can also be engineered to express CAR, and such CAR-TILs could be dual-targeting. To this end, tumor samples and autologous TILs from metastasized human uveal and cutaneous melanoma were expanded in vitro and transduced with a lentiviral vector encoding an anti-HER2 CAR construct. When infused into patient-derived xenograft (PDX) mouse models carrying autologous tumors, CAR-TILs were able to eradicate melanoma, even in the absence of antigen presentation by HLA. To advance this concept to the clinic and assess its safety in an immune-competent and human-patient-like setting, we treated four companion dogs with autologous anti-HER2 CAR-TILs. We found that these cells were tolerable and showed signs of anti-tumor activity. Taken together, CAR-TIL therapy is a promising avenue for broadening the tumor-targeting capacity of TILs in patients with checkpoint immunotherapy-resistant melanoma

A patient-derived xenograft pre-clinical trial reveals treatment responses and a resistance mechanism to karonudib in metastatic melanoma

Karonudib (TH1579) is a novel compound that exerts anti-tumor activities and has recently entered phase I clinical testing. The aim of this study was to conduct a pre-clinical trial in patient-derived xenografts to identify the possible biomarkers of response or resistance that could guide inclusion of patients suffering from metastatic melanoma in phase II clinical trials. Patient-derived xenografts from 31 melanoma patients with metastatic disease were treated with karonudib or a vehicle for 18 days. Treatment responses were followed by measuring tumor sizes, and the models were categorized in the response groups. Tumors were harvested and processed for RNA sequencing and protein analysis. To investigate the effect of karonudib on T-cell-mediated anti-tumor activities, tumor-infiltrating T cells were injected in mice carrying autologous tumors and the mice treated with karonudib. We show that karonudib has heterogeneous anti-tumor effect on metastatic melanoma. Thus, based on the treatment responses, we could divide the 31 patient-derived xenografts in three treatment groups: progression group (32%), suppression group (42%), and regression group (26%). Furthermore, we show that karonudib has anti-tumor effect, irrespective of major melanoma driver mutations. Also, we identify high expression of ABCB1, which codes for p-gp pumps as a resistance biomarker. Finally, we show that karonudib treatment does not hamper T-cell-mediated anti-tumor responses. These findings can be used to guide future use of karonudib in clinical use with a potential approach as precision medicine

Investigating dietary life histories and mobility of children buried in St Gertrude Church Cemetery, Riga, Latvia (15th– 17th centuries AD)

Carbon and nitrogen isotope profiles were obtained from incremental dentine analysis of 19 non‐adults from a cemetery in Riga, Latvia. The research compared the life histories and diet between people buried in two mass graves and the general cemetery. The δ13C profiles of several children from the mass graves were similar but did not resemble the patterns seen in children from the general cemetery, suggesting that they probably represented a different population group. The rise in δ15N values towards the end of the life of four individuals from one mass grave suggests they were victims of an historically documented famine