Miracle-dz/UniFAR-FTUs huggingface dataset:
MEN1309/OBT076, a first-in-class Antibody-drug Conjugate (ADC) targeting CD205 in solid tumors.

CD205 is a type I transmembrane glycoprotein, member of C-type lectin receptor family. Analysis by mass spectrometry revealed that CD205 was robustly expressed and highly prevalent in a variety of solid malignancies from different histotypes. Immunohistochemistry (IHC) confirmed the increased expression of CD205 in pancreatic, bladder and triple negative breast cancer (TNBC) compared to that in the corresponding normal tissues. Using immunofluorescence microscopy, rapid internalization of the CD205 antigen was observed. These results supported the development of MEN1309/OBT076, a fully humanized CD205-targeting monoclonal antibody conjugated to DM4, a potent maytansinoid derivate, via a cleavable N-succinimidyl-4-(2-pyridyldithio) butanoate linker. MEN1309/OBT076 was characterized in vitro for target binding affinity, mechanism of action and cytotoxic activity against a panel of cancer cell lines. MEN1309/OBT076 displayed selective and potent cytotoxic effects against tumor cells exhibiting strong and low to moderate CD205 expression. In vivo MEN1309/OBT076 showed potent antitumor activity resulting in durable responses and complete tumor regressions in many TNBC, pancreatic, and bladder cancer cell-line derived and patient-derived xenograft (PDX) models, independent of antigen expression levels. Finally, the pharmacokinetics (PK) and pharmacodynamic (PD) profile of MEN1309/OBT076 was characterized in pancreatic tumor bearing mice demonstrating the serum level of ADC achieved through dosing was consistent with the kinetics of its anti-tumor activity. Overall, our data demonstrate that MEN1309/OBT076 is a novel and selective antibody-drug conjugate (ADC) with potent activity against CD205 positive tumors. These data supported the clinical development of MEN1309/OBT076 and further evaluation of this ADC is currently ongoing in the first-in-human Our results highlight characteristics of CD205, such as differential cell surface expression in multiple human cancers compared to healthy tissues and a rapid internalization rate, that indicate this antigen may be an ideal target for an ADC therapy. Herein, we discuss the activity of a new The molecule consists of a novel anti-CD205 human antibody conjugated a cleavable N-succinimidyl-4-(2-pyridyldithio) is a selective and promising first-in-class antitumor ADC. Together with an acceptable toxicity profile in relevant preclinical species, these data supported the start of the first-in-human SHUTTLE study (NCT03403725) in CD205-positive metastatic solid tumors and relapsed or refractory non-Hodgkin’s lymphoma patients.
Diurnal cycle of surface winds over the subtropical southeast Pacific

[1] The diurnal variability of surface winds over the SE Pacific is characterized with QuikSCAT data for years 2000–2006. The twice daily satellite passes occur around 0600 and 1800 LT (referred to as AM and PM, respectively). The PM-AM wind difference maximizes in a region between 20°S and 30°S, extending from the Chilean coast up to 75°W. This difference is mostly meridional (along the coast) with seasonal variation characterized by summertime weakening of the morning winds. The observational analysis is supplemented with mesoscale model results for December 2003. They show that the coastal zonal flow increases between 0600 and 1200 local time (LT) but then decreases in the next 6 hours, which explains the absence of an onshore component in the QuikSCAT PM-AM difference. Additional model diagnostics show that in this region the diurnal cycle hodographs are more simple and larger above the marine boundary layer (MBL) than at the surface. Evaluation of the momentum and temperature budgets reveals the importance of the diurnal cycle of vertical velocity coupled with the thermal structure in controlling the diurnal cycle of the low-level winds. Around 1300 LT coastal subsidence maximizes in a layer sloping from 1000 m at 36°S to 3000 m at 22°S, inducing the development of a coastal trough at the surface. During the night the passage of a high-pressure perturbation reverses the surface meridional pressure gradient force, inducing the decrease of the coastal meridional winds. These results stress the important role played by the dynamics of the low troposphere above the MBL (e.g., the heating of the Andes Cordillera to the east) in controlling the wind diurnal cycles near the surface.
Epidemiology and Outcomes of Achilles Tendon Ruptures in the National Football League

The purpose of this study is to document the epidemiology of Achilles tendon ruptures in the National Football League (NFL) and to quantify the impact of these injuries on player performance. A retrospective review of several online NFL player registries identified 31 Achilles tendon ruptures in NFL players between 1997 and 2002. Nineteen percent of injuries occurred during preseason play, while another 18% occurred during the first month of the official season. There was a postinjury reduction of 88%, 83%, and 78% in power ratings for wide receivers, running backs, and tight ends, respectively, over a 3-year period. There was a 95%, 87%, and 64% postinjury reduction in power ratings for linebackers, cornerbacks, and defensive tackles over a 3-year period. On average, players experienced a greater than 50% reduction in their power ratings following such an injury. Thirty-two percent (n = 10) of NFL players who sustained an Achilles tendon rupture did not return to play in the NFL.
PATHOBIOLOGY of MARINE and ESTUARINE ORGANISMS

The book is an up-to-date compendium of scientific findings related to diseases of marine and estuarine organisms. The information was presented at the Gulf Breeze Symposium on Marine and Estuarine Disease Research sponsored by the U.S. Environmental Protection Agency (EPA) Environmental Monitoring and Assessment Program (EMAP) held in October 1990 on Pensacola Beach, Florida. Authors review the state-of-the-science and recommend research for future studies of the impact of xenobiotics and other anthropogenic stress factors on disease processes in marine and estuarine organisms.
RESPIRATORY VIRUSES AND CLINICAL- EPIDEMIOLOGICAL CHARACTERISTICS IN EPISODES OF ACUTE RESPIRATORY INFECTION

The aim of the study was to determine the viral frequency and clinical-epidemiological characteristics in the episodes of acute respiratory infection in patients of the Instituto Nacional de Salud del Niño San Borja in Lima, the information of the episodes of patients who required at least one direct Immunofluorescence test from January 1, 2017 to December 31, 2018 was analyzed. 1153 episodes were identified in 707 patients. The median age was 1 year and 55% were male. The viral frequency was 13.4%; respiratory syncytial virus was identified in 10.7% of the episodies. The viral frequency was higher in children under 1 year of age (16.2%); in those with congenital disease respiratory (38.9%) and during the autumn (24.2%). The most common symptoms were cough (70.3%) and fever (53.4%); and the main diagnoses, viral pneumonia (31.8) and bronchiolitis (23.4%). It is concluded that the respiratory viral frequency was related to age, seasonality and pre-existing pathology.
Active Tectonics of the Pyrenees: a review

The Pyrenees have experienced at least seven earthquakes with magnitude M > 5 in the last 400 years. During the last decades, several seismotectonic, neotectonic and paleoseismological studies have focused on identifying the main active structures of the areas experiencing damaging earthquakes. In spite of these studies, the regional stress regime is still discussed and there is no unequivocal seismotectonic model at the scale of the range. In this paper, we first present a revision of the former works on active faults in the Pyrenees, and then we discuss the main results in terms of their neotectonic setting. We have distinguished five neotectonic regions according to their seismicity, faulting style and morphologic evolution: the westernmost Pyrenees, the North Western Pyrenean zone, the Foreland basins, the Lower Thrust Sheets Domain and the Eastern Pyrenees. This review lead us to differentiate the range into two major domains: the High Chain, where active faults are controlled by vertical maximum stresses, and the Low Chain, where horizontal maximum stresses of variable orientation seem to be dominant. We propose that these different stress domains are related to the isostatic rebound in response to either the difference in crustal thickness and/or the distribution of the Plio-Quaternary erosion.
Current condition of tobacco soils of Lázaro Peña enterprise in Artemisa province.

During the last 20 years the science of soil has worked on the soil degradation. The Red Ferralitic Soils of "Lazaro Pena" enterprise are not excluded of this process as they are extremely subjected to an intensive cultivation, which causes alterations of its chemical and physical - chemical properties. The diagnostic of these processes allows to design strategies for its recovery, so that this work has the objective to characterize since the physical and chemical points of view the soils of this enterprise. For this reason samples of soils of each Basic Units of Cooperative Production of the enterprise were taken and the correspondent analisys at Research Tobacco Institute were carried out. The results showed high value of pH on the soils which constitutes a limit for tobacco production due to the requirements of tobacco plant. Besides the content of organic matter are low in spite of proving an increase which improves the levels of soil fertility. An unfavourable calcium / magnesium and relationship is shown as a a result of an intensive tobacco cultivation because the irrigation is carried out with hard water which limits besides limits the absorption of magnesium due to they are antagonistic elements. The phosphorus and potassium values are suitable for these soils. As conclusion, there is a high Ca/Mg relationship and reaction of the soil , that suggests to search of new alternatives for improvement and conservation of the soils.
Floodplain biogeochemical processing of floodwaters in the Atchafalaya River Basin during the Mississippi River flood of 2011

The 2011 flood in the Lower Mississippi resulted in the second highest recorded river flow diverted into the Atchafalaya River Basin (ARB). The higher water levels during the flood peak resulted in high hydrologic connectivity between the Atchafalaya River and floodplain, with up to 50% of the Atchafalaya River water moving off channel. Water quality samples were collected throughout the ARB over the course of the flood event. Significant nitrate (NO3−) reduction (75%) occurred within the floodplain, resulting in a total NO3− reduction of 16.6% over the flood. The floodplain was a small but measurable source of dissolved reactive phosphorus and ammonium (NH4+). Collectively, these results from this large flood event suggest that enhancing river‐floodplain connectivity through freshwater diversions will reduce NO3− loads to the Gulf of Mexico during large annual floods.
Forest ecosystem changes from annual methane source to sink depending on late summer water balance

Forests dominate the global carbon cycle, but their role in methane (CH4) biogeochemistry remains uncertain. We analyzed whole‐ecosystem CH4 fluxes from 2 years, obtained over a lowland evergreen forest in Maine, USA. Gross primary productivity provided the strongest correlation with the CH4 flux in both years, with an additional significant effect of soil moisture in the second, drier year. This forest was a neutral to net source of CH4 in 2011 and a small net sink in 2012. Interannual variability in the summer hydrologic cycle apparently shifts the ecosystem from being a net source to a sink for CH4. The small magnitude of the CH4 fluxes and observed control or CH4 fluxes by forest productivity and summer precipitation provide novel insight into the CH4 cycle in this globally important forest ecosystem.
Venom-gland Transcriptomic, Venomic, and Antivenomic Pro�les of the Spine-bellied Sea Snake (Hydrophis curtus) from the South China Sea

Background: A comprehensive evaluation of the -omic pro�les of venom is important for understanding the potential function and evolution of snake venom. Here, we conducted an integrated multi-omics-analysis to unveil the venom-transcriptomic and venomic pro�les in a same group of spine-bellied sea snakes (Hydrophis curtus) from the South China Sea, where the snake is a widespread species and might generate regionally-speci�c venom potentially harmful to human activities. The capacity of two heterologous antivenoms to immunocapture the H. curtus venom was determined for an in-depth evaluation of their rationality in treatment of H. curtus envenomation. In addition, a phylogenetic analysis by maximum likelihood was used to detect the adaptive molecular evolution of full-length toxin-coding unigenes. Results: A total of 90,909,384 pairs of clean reads were generated via Illumina sequencing from a pooled cDNA library of six specimens, and yielding 148,121 unigenes through de novo assembly. Sequence similarity searching harvested 63,845 valid annotations, including 63,789 non-toxin-coding and 56 toxin-coding unigenes belonging to 22 protein families. Three protein families, three-�nger toxins (3-FTx), phospholipase A 2 (PLA 2 ), and cysteine-rich secretory protein, were detected in the venom proteome. 3-FTx (27.15% in the transcriptome/41.94% in the proteome) and PLA 2 (59.71%/49.36%) were identi�ed as the most abundant families in the venom-gland transcriptome and venom proteome. In addition, 24 unigenes from 11 protein families were shown to have experienced positive selection in their evolutionary history, whereas four were relatively conserved throughout evolution. Commercial Naja atra antivenom exhibited a stronger capacity than Bungarus multicinctus antivenom to immunocapture H. curtus venom components, especially short neurotoxins, with the capacity of both antivenoms to immunocapture short neurotoxins being weaker than that for PLA 2 s. Conclusions: Our study clari�ed the venom-gland transcriptomic and venomic
AKT regulates mitotic progression of mammalian cells by phosphorylating MASTL

Microtubule associated serine threonine like kinase (MASTL) has been recently identified as an important regulator of mitosis. By inhibiting protein phosphatase 2A, it plays a crucial role in activating one of the most important mitotic kinases known as cyclin dependent kinase1 (CDK1). MASTL has been seen to be up regulated in various types of cancers and is involved in tumor recurrence. It is activated by CDK1 through its auto regulatory loop but the complete mechanism of its activation is still unclear. In this study, we evaluated the regulation of MASTL via AKT during mitosis. Here we report that AKT phosphorylates MASTL at T299 which plays a critical role in its activation. Our results suggest that AKT increases CDK1 mediated phosphorylation and hence activity of MASTL which in turn promotes cell proliferation. We also show that the oncogenic potential of AKT is augmented by MASTL activation as the AKT mediated oncogenesis in colorectal cell lines can be attenuated by inhibiting and/or silencing MASTL. In brief, we report that AKT has an important role in the progression of mitosis in mammalian cells and it does so through the phosphorylation and activation of MASTL.
Maternal obesity induces gut inflammation and impairs gut epithelial barrier function in non-obese diabetic (NOD) mice

Impairment of gut epithelial barrier function is a key predisposing factor for inflammatory bowel disease, type 1 diabetes (T1D), and related autoimmune diseases. We hypothesized that maternal obesity induces gut inflammation and impairs epithelial barrier function in the offspring of non-obese diabetic (NOD) mice. 4-week-old female NOD /ShiLtJ mice were fed with a control diet (CON, 10% energy from fat) or a high fat diet (HFD, 60% energy from fat) for 8 weeks to induce obesity and then mated. During pregnancy and lactation, mice were maintained in their respective diets. After weaning, all offspring were fed the CON diet. At 16 weeks of age, female offspring were subjected to in vivo intestinal permeability test and, then, ileum was sampled for biochemical analyses. Inflammasome mediators, activated caspase-1 as well as mature forms of interleukin (IL) -1 β and IL-18 were enhanced in offspring of obese mothers, which was associated with elevated serum tumor necrosis factor (TNF) α level and inflammatory mediators. Consistently, abundance of oxidative stress markers including catalase, peroxiredoxin-4 and superoxide dismutase 1 were heightened in offspring ileum ( P < 0.05). Furthermore, offspring from obese mothers had a higher intestinal permeability. Morphologically, maternal obesity reduced villi/ crypt ratio in the ileum of offspring gut. In conclusion, maternal obesity induced inflammation and impaired gut barrier function in offspring of NOD mice. The enhanced gut permeability
Morphological Monitoring of a High Energy Beach System Using GPS and Total Station Techniques, Runkerry, Co. Antrim, Northern Ireland

ABSTRACT Methodological aspects of GPS (Global Positioning System) and Total Station (Electronic Distance Measurement) surveying techniques were examined as part of a beach monitoring programme which was used to assess morphological variation of a high-energy beach system at Runkerry, Co.Antrim, Northern Ireland. The accuracy of the instruments as well as data processing methods concerning data conversion in different plane coordinates systems is discussed. GPS with Real Time Kinematics (RTK) provides high-resolution control on topographical surveying within limits on the order of centimeter-level accuracy in the horizontal and 2 cm in vertical dimension. Total station (EDM) also demonstrated high accuracy during its use in the monitoring programme. The model of EDM used in this work had a 5 to 6 degrees offset angle for the orientation due to the inherent characteristics of the instrument. A threshold-narrowed point selecting treatment was used to form a beach profile point set for the profile plot and any further processing. This work demonstrates that a two-dimensional translation and rotation for horizontal dimension data conversion is preferable over linear regression method; while the linear regression method for the vertical dimension data is still acceptable. It is suggested therefore that when a conversion of beach surveying data from one plane coordinate system to another is required, then this combined approach should be adopted in the analysis.
Rain day frequency and mean daily rainfall intensity as determinants of total rainfall over the eastern Orange free state

Summer rainfall totals over the eastern Orange Free State are described in terms of number of days of rain and of mean rainfall per rain day. Variations in rainfall may be considered to result from frequency changes in an objectively-chosen subset of significant rain days. It is demonstrated, through the use of the equation y = αx exp (βx) (where x and y are the cumulative percentages of the number of rain days and of the rainfall respectively), that increases in mean rainfall per rain day result from an increased number of, and increased intensity of rain on, the heaviest rain days. Some implications of these findings for studies of atmospheric circulation changes and for weather modification are discussed.
Water and climate change : impacts on groundwater resources and adaptation options

Adaptation to climate impacts on groundwater resources in developed and developing countries has not received adequate attention. This reflects the often poorly understood impacts of climate change, the hidden nature of groundwater and the general neglect of groundwater management. Many developing countries are highly reliant on groundwater. Given expectations of reduced supply in many regions and growing demand, pressure on groundwater resources is set to escalate. This is a crucial problem and demands urgent action. This report addresses the impacts of climate change on groundwater and adaptation options. The Earth's climate is projected to become warmer and more variable. Increased global temperatures are projected to affect the hydrologic cycle, leading to changes in precipitation patterns and increases in the intensity and frequency of extreme events; reduced snow cover and widespread melting of ice; rising sea levels; and changes in soil moisture, runoff and groundwater recharge. Increased evaporation and the risk of flooding and drought could adversely affect security of water supply, particularly surface water. Due to these pressures, as well as global population growth, demand for groundwater is likely to increase.
Where and how do young People Like to Get their Sexual and Reproductive Health Information? Experiences from Students in Higher Learning Institutions in Tanzania: A Cross-sectional Study

Background Sexual and reproductive health (SRH) among young adults in developing countries is still a major public health concern. Early school-based sexuality education programs and sexual health information sharing between teachers, parents and young people have been considered protective against sexual health risks that young people are prone to. There is limited information on preferred choices of “where” and “how” young people like to get their SRH information. Here, we describe what young people prefer to learn with regard to sexual matters, where and who they prefer to learn from, and their experiences of parent-child sexuality communication. MethodsThis was a cross-sectional study, conducted from March 2019 to January 2020 among students aged 18-24 years attending Higher Learning Institutions (HLIs) within Mbeya. A self-administered questionnaire was used to collect information on SRH education, ability to discuss sexual matters with a parent/guardian, and SRH information gap during early sexual experience. ResultsOut of 504 students that were enrolled, 377 (74.8%) reported to be sexually active with mean age at sexual debut of 18.4 years. Six out of ten students found it difficult to discuss or did not discuss sexual matters with a parent/guardian while growing up at age 12-18 years. Majority learnt about SRH matters from peers (30%) and lessons at schools (23%). We found a gender-biased preference on sexual matters discussions, such that female and male participants preferred discussions with female adults and male adults, respectively. Peers (18%), Media (17%) and schools (13%) were preferred sources of SRH information. On recalling first sexual experience, participants felt they needed to know more about sexual feelings, emotions and relationships (26.9%), safer sex (13.8%), how to be able to say 'No' (10.5%) and how to use a condom correctly (10.2%). ConclusionYoung people have a gender-biased preference when it comes to learning about SRH matters from their parents; however, such conversations seldom occur. Community health IEC should incorporate the agenda on building skills of parents on parent-child communication on sexual matters so as to empower them to confidently initiate and convey appropriate and sufficient sexual health information. Comprehensive SRH education and skills building is needed in the current school SRH curriculum in order need to meet the demand and needs of students’ and teachers’.