Landscape evolution of the Apurimac river drainage basin, southern Peru

The northernmost part of the Altiplano in Southern Peru is drained by the river Apurimac and its tributaries. The Altiplano is a region that covers most of the eastern part of the Cordillera Occidental and is bounded in the East by the Cordillera Oriental. The Apurirnac River Drainage Basin (ARDB) extends roughly between 13 °S and l5°S over 50000 km 2. It mainly occupies the northeastern flank of the Cordillera Occidental and a negligible part of the southwestern flank of the Cordillera Oriental. At the latitude of the Abancay deflection, i.e. 13.5 S; 72.7 W, the Apurirnac River abandons the Cordillera Occidental. On its way to the Amazon Basin in the North the Apurimac River drains the Cordillera Oriental and the Sub-Andean Zone (SAZ). The incision by the rivers of the ARDB has created differences in relief of more than 2000 m that contributed to the denudation and exhumation, hence the evolution ofthe landscape. The Altiplano sedimentary basin contains an 8 kilometers thick succession of Cenozoic sediments, which it received from the surrounding highs in the West and the Easl Its structural framework has been formed by the various tectonic events that struck the Andes and the various pulses of magmatic activity that took place during the Cenozoic. In the western part of the Altiplano Miocene volcanics domínate, whereas in the northeastern part, in the Cusco region, clastic deposits do so. In the region of Abancay, a batholite got emplaced during the mid Tertiary, that extends over few 1000 km2

Apparent Lack of BRAFV600E Derived HLA Class I Presented Neoantigens Hampers Neoplastic Cell Targeting by CD8+ T Cells in Langerhans Cell Histiocytosis

Langerhans Cell Histiocytosis (LCH) is a neoplastic disorder of hematopoietic origin characterized by inflammatory lesions containing clonal histiocytes (LCH-cells) intermixed with various immune cells, including T cells. In 50-60% of LCH-patients, the somatic BRAFV600E driver mutation, which is common in many cancers, is detected in these LCH-cells in an otherwise quiet genomic landscape. Non-synonymous mutations like BRAFV600E can be a source of neoantigens capable of eliciting effective antitumor CD8+ T cell responses. This requires neopeptides to be stably presented by Human Leukocyte Antigen (HLA) class I molecules and sufficient numbers of CD8+ T cells at tumor sites. Here, we demonstrate substantial heterogeneity in CD8+ T cell density in n = 101 LCH-lesions, with BRAFV600E mutated lesions displaying significantly lower CD8+ T cell:CD1a+ LCH-cell ratios (p = 0.01) than BRAF wildtype lesions. Because LCH-lesional CD8+ T cell density had no significant impact on event-free survival, we investigated whether the intracellularly expressed BRAFV600E protein is degraded into neopeptides that are naturally processed and presented by cell surface HLA class I molecules. Epitope prediction tools revealed a single HLA class I binding BRAFV600E derived neopeptide (KIGDFGLATEK), which indeed displayed strong to intermediate binding capacity to HLA-A*03:01 and HLA-A*11:01 in an in vitro peptide-HLA binding assay. Mass spectrometry-based targeted peptidomics was used to investigate the presence of this neopeptide in HLA class I presented peptides isolated from several BRAFV600E expressing cell lines with various HLA genotypes. While the HLA-A*02:01 binding BRAF wildtype peptide KIGDFGLATV was traced in peptides isolated from a

How to bring a technical artifact into use: A micro-developmental perspective

In order to understand how technical artifacts are attuned to, interacted with, and shaped in various and varied classrooms, it is necessary to construct detailed accounts of the use of particular artifacts in particular classrooms. This paper presents a descriptive account of how a shared workspace was brought into use by a student pair in a face-to-face planning task. A micro-developmental perspective was adopted to describe how the pair established a purposeful connection with this unfamiliar artifact over a relatively short time frame. This appropriation was examined against the background of their regular planning practice. We describe how situational resources present in the classroom—norms, practices and artifacts— frame possible action, and how these possibilities are enacted by the pair. Analysis shows that the association of norms and practices with the technical artifact lead to a contradiction that surfaced as resistance experienced from the artifact. This resistance played an important part in the appropriation process of the pair. It signaled tension in the activity, triggered reflection on the interaction with the artifact, and had a coordinative function. The absence of resistance was equally important. It allowed the pair to transpose or depart from regular procedure without reflection

Steady-state exhumation pattern in the Central Andes – SE Peru

The Western Cordillera of SE Peru is part of the Central Andes and is situated to the west of the Eastern Andes from which it is separated by the northern termination of the Altiplano – the Inter-Andean Valley. It is a volcanic–volcano-detrital chain that developed in the Palaeogene, and is characterized by a 4000 m-high mean altitude whose origin is poorly constrained. We selected a vertical profile in the region of Abancay to trace the record the evolving uplift and erosion history of the Andean orogen. Fission-track data on both apatite and zircon crystals were completed on plutonic rocks of the Tertiary Andahuaylas–Yauri batholith. Ages ranged between 24 and 14 Ma, and 38 and 30 Ma, respectively. Thermal modelling was completed for the whole profile and does not, like age–altitude relationships, show evidence of any clear disruption of the exhumation paths since 38 Ma either by sedimentary burial and/or rapid exhumation. One of the noteworthy aspects of the data is that exhumation was steady at a rate of 0.17 km Ma-1 from the late Eocene until at least the middle Miocene (38–14 Ma). The uplift of the Western Cordillera was thus probably steady for this period with sedimentary deposition restricted to the present-day Altiplano and Inter-Andean Valley regions

Outcomes of surgical resections for benign colon polyps: A systematic review

Background Not all benign colonic polyps are suitable for endoscopic resection, although criteria for endoscopic non-resectability vary worldwide. Clinical decision-making largely depends on endoscopic treatment options, as well as postoperative risks after surgical resection. This systematic review aimed to determine postoperative outcomes and the characteristics of surgically resected benign colonic polyps. Methods MEDLINE, EMBASE, and the Cochrane Library were searched for studies investigating the outcomes of surgical resection for benign colonic polyps since 1980. Studies were considered eligible when at least one postoperative outcome (morbidity and/or mortality) was reported. Meta-analyses were conducted for the primary outcome measures (morbidity and mortality) for studies that included patients only after the year 2000. Results Of the 4210 studies retrieved, 26 studies describing 139 897 patients were included. The most common indications for surgical resection were polyp location in the right-sided colon, non-pedunculated morphology, and large polyp size. The pooled 1-month complication and mortality rates of studies that included patients after the year 2000 were 24 % (95 % confidence interval [CI] 15 % - 36 %) and 0.7 % (95 %CI 0.6 % - 0.8 %), respectively. Conclusion The postoperative morbidity and mortality after colonic resection for benign polyps are substantial. Referral to an advanced interventional endoscopist should be considered before referral for surgery to evaluate the possibilities for endoscopic treatment of large, non-pedunculated, and/or colonic polyps in difficult locations without suspicion of submucosal malignant invasion

Detection of Sepsis in Preterm Infants by Fecal Volatile Organic Compounds Analysis:A Proof of Principle Study

Objectives: Several studies associated altered gut microbiota composition in preterm infants with late-onset sepsis (LOS), up to days before clinical onset of sepsis. Microbiota analysis as early diagnostic biomarker is, however, in clinical practice currently not feasible because of logistic aspects and high costs. Therefore, we hypothesized that analysis of fecal volatile organic compounds (VOCs) may serve as noninvasive biomarker to predict LOS at a preclinical stage, because VOC reflect the composition and activity of intestinal microbial communities. Methods: In a prospective multicenter study, fecal samples were collected daily from infants with a gestational age of <30 weeks. VOC signatures of fecal samples from infants with LOS, collected up to 5 days before diagnosis, were analyzed by means of an electronic nose technology (Cyranose 320) and compared to matched controls. Results: Fecal VOC profiles of infants with LOS (n = 36) could be discriminated from controls (n = 40) at 3 days (area under the curve [+/- 95% confidence interval], P value, sensitivity, specificity; 70.2 [52.2-88.3], 0.033, 57.1%, 61.5%), 2 days (77.7 [62.7-92.7], 0.050, 75.0%, 70.8%), and 1 day (70.4 [49.6-91.3], 0.037, 64.3%, 64.3%) before the onset of LOS. Conclusions: Fecal VOC profiles of preterm infants with LOS could be discriminated from matched controls, up to 3 days before clinical onset of the disease, underlining the hypothesis that intestinal microbiota may play an etiological role in LOS. Notably, VOC profiling is clinically feasible and the potential of this technique in the early detection of LOS needs to be confirmed in future studie