Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting KRAS for the potential treatment of pancreatic ductal adenocarcinoma: Recent advancements provide hope (Review)

Kirsten rat sarcoma viral oncogene homolog (KRAS) is one of the most frequently mutated oncogenes in solid tumors. More than 90% of pancreatic ductal adenocarcinoma (PDAC) are driven by mutations in the KRAS gene, suggesting the importance of targeting this oncogene in PDAC. Initial efforts to target KRAS have been unsuccessful due to its small size, high affinity for guanosine triphosphate/guanosine diphosphate, and lack of distinct drug-binding pockets. Therefore, much of the focus has been directed at inhibiting the activation of major signaling pathways downstream of KRAS, most notably the PI3K/AKT and RAF/MAPK pathways, using tyrosine kinase inhibitors and monoclonal antibodies. While preclinical studies showed promising results, clinical data using the inhibitors alone and in combination with other standard therapies have shown limited practicality, largely due to the lack of efficacy and dose-limiting toxicities. Recent therapeutic approaches for KRAS-driven tumors focus on mutation-specific drugs such as selective KRASG12C inhibitors and son of sevenless 1 pan-KRAS inhibitors. While KRASG12C inhibitors showed great promise against patients with non-small cell lung cancer (NSCLC) harboring KRASG12C mutations, they were not efficacious in PDAC largely because the major KRAS mutant isoforms in PDAC are G12D, G12V, and G12R. As a result, KRASG12D and pan-KRAS inhibitors are currently under investigation as potential therapeutic options for PDAC. The present review summarized the importance of KRAS oncogenic signaling, challenges in its targeting, and preclinical and clinical targeted agents including recent direct KRAS inhibitors for blocking KRAS signaling in PDAC.
The Relationships between Employees Perceptions of Organizational Justice, HR Attributions, and Affective Organizational Commitment

Purpose –The purpose of this study is to test Nishii et al.’s (2008) HR attributions theory with respect to explaining how individual variability in HR perceptions shapes work attitudes.Design/methodology/approach –Online surveys were sent to the organizational clients of a business consulting company operating in Turkey. Correspondents from organizations were asked to send the forms to a random group among their employees. Survey responses were received from 116 employees from 19 companies. The main and interactive effects of independent variables were tested using moderated multiple regression analyses conducted with SPSS Process macro (Hayes, 2012). Findings –The results supported the hypothesis that there is a positive relationship between employees’ perceptions of organizational justice and affective commitment. Furthermore, as expected, employees’ well-being and service quality HR attributions were found to be positively related to commitment, whereas union compliance HR attribution was negatively related to commitment. Cost-cutting and exploitation HR attributions were not found to be significantly related to commitment. Lastly, it was found that the relationship between justice perceptions and organizational commitment was moderated by only one of the five types of HR attributions, namely employee exploitation attribution. Hence, the moderation hypothesis was partially supported. Discussion –This study explained and provided empirical support for the role of employees’ perceptions of causal HR attributions as an important antecedent and regulator of organizational commitment. This implies that organizations should pay attention to understanding, managing, and maintaining employees’ idiosyncratic perceptions about the rationale behind the adoption of HR practices. Future research is needed to investigate other potential antecedents and outcomes of these HR attributions.
Memantine increases the dendritic complexity of hippocampal young neurons in the juvenile brain after cranial irradiation

Introduction Cranial irradiation (IR) negatively regulates hippocampal neurogenesis and causes cognitive dysfunctions in cancer survivors, especially in pediatric patients. IR decreases proliferation of neural stem/progenitor cells (NSPC) and consequently diminishes production of new hippocampal neurons. Memantine, an NMDA receptor antagonist, used clinically to improve cognition in patients suffering from Alzheimer’s disease and dementia. In animal models, memantine acts as a potent enhancer of hippocampal neurogenesis. Memantine was recently proposed as an intervention to improve cognitive impairments occurring after radiotherapy and is currently under investigation in a number of clinical trials, including pediatric patients. To date, preclinical studies investigating the mechanisms underpinning how memantine improves cognition after IR remain limited, especially in the young, developing brain. Here, we investigated whether memantine could restore proliferation in the subgranular zone (SGZ) or rescue the reduction in the number of hippocampal young neurons after IR in the juvenile mouse brain. Methods Mice were whole-brain irradiated with 6 Gy on postnatal day 20 (P20) and subjected to acute or long-term treatment with memantine. Proliferation in the SGZ and the number of young neurons were further evaluated after the treatment. We also measured the levels of neurotrophins associated with memantine improved neural plasticity, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Results We show that acute intraperitoneal treatment with a high, non-clinically used, dose of memantine (50 mg/kg) increased the number of proliferating cells in the intact brain by 72% and prevented 23% of IR-induced decrease in proliferation. Long-term treatment with 10 mg/kg/day of memantine, equivalent to the clinically used dose, did not impact proliferation, neither in the intact brain, nor after IR, but significantly increased the number of young neurons (doublecortin expressing cells) with radial dendrites (29% in sham controls and 156% after IR) and enhanced their dendritic arborization. Finally, we found that long-term treatment with 10 mg/kg/day memantine did not affect the levels of BDNF, but significantly reduced the levels of NGF by 40%. Conclusion These data suggest that the enhanced dendritic complexity of the hippocampal young neurons after treatment with memantine may contribute to the observed improved cognition in patients treated with cranial radiotherapy.
Paleogene Extension in the Southern Basin and Range Province of Mexico: Syndepositional Tilting of Eocene Red Beds and Oligocene Volcanic Rocks in the Guanajuato Mining District

The Guanajuato region, located in the southern part of the Basin and Range tectonic province, is characterized by a rhombohedral fault pattern. Extensional faulting-as well as related uplift, erosion, and deposition of continental clastic deposits-was in progress at 49 Ma, as indicated by K-Ar dating of intercalated mafic volcanic lavas. Earliest extension is registered in the lower member of the Guanajuato conglomerate and produced NW-trend-ing, down to the southwest, normal faults and northeast tilting of the hanging-wall clastic sequence. Beds in the upper member of the Guanajuato conglomerate display lateral thickness variations, changes in size and composition of the clasts, and ENE and SE inclination, all of which suggest activity along a second set of NE-trending younger faults. Extension continued also after emplacement of the overlying Bufa ignimbrite (∼37 Ma, K-Ar). Dip differences between the conglomerate and the Calderones Formation ( 30 Ma), which is part of the volcanic sequence that.
When will the summer Arctic be nearly sea ice free?

The observed rapid loss of thick multiyear sea ice over the last 7 years and the September 2012 Arctic sea ice extent reduction of 49% relative to the 1979–2000 climatology are inconsistent with projections of a nearly sea ice‐free summer Arctic from model estimates of 2070 and beyond made just a few years ago. Three recent approaches to predictions in the scientific literature are as follows: (1) extrapolation of sea ice volume data, (2) assuming several more rapid loss events such as 2007 and 2012, and (3) climate model projections. Time horizons for a nearly sea ice‐free summer for these three approaches are roughly 2020 or earlier, 2030 ± 10 years, and 2040 or later. Loss estimates from models are based on a subset of the most rapid ensemble members. It is not possible to clearly choose one approach over another as this depends on the relative weights given to data versus models. Observations and citations support the conclusion that most global climate model results in the CMIP5 archive are too conservative in their sea ice projections. Recent data and expert opinion should be considered in addition to model results to advance the very likely timing for future sea ice loss to the first half of the 21st century, with a possibility of major loss within a decade or two.
Simulation of an Aggressive Slip Sweep Scheme In the Western Desert, Egypt

Repsol-YPF and Schlumberger simulated an aggressive 3D slip sweep test in the Western Desert of Egypt, where field records are dominated by source generated noise. The results support previous findings (Rozemond, 1996) that the slip sweep method – properly implemented does not cause a deterioration in final data quality. The parameter “slip time” can, therefore, be treated as just one more, routine, optimisation factor for vibroseis 3D surveys.
Detection of an observed 135 year ocean temperature change from limited data

Recent work comparing historical hydrographic data with modern Argo observations shows a long‐term change in the global ocean temperature. The magnitude of this change is greater than estimates of late 20th century warming, and implies a century‐scale change in the global oceans. Using global coupled climate models from the Coupled Model Intercomparison Project Phase 5 suite of simulations, we assess to what extent this observed temperature difference can be attributed to a genuine long‐term warming trend. After accounting for natural variability and sampling errors, we find convincing evidence that there has indeed been a century‐scale anthropogenic warming of the global ocean up to the present day, and a strong possibility of anthropogenic warming from 1873 to 1955. The estimated 1873–1955 ocean warming implies a net top‐of‐atmosphere energy imbalance of 0.1 ± 0.06 Wm–2, and a thermosteric global mean sea level rise of 0.50 ± 0.2 mma–1.
Late Pleistocene–Holocene records from Lake Ulaan, southern Mongolia: implications for east Asian palaeomonsoonal climate changes

A 5.88‐m‐long core taken from Lake Ulaan was studied for high‐resolution paleoclimatic changes during the last 17 000 years. The core sediments are divided into three units based on grain‐size distribution: unit 1 (top to 392 cm depth, covering the last 11 200 years), unit 2 (392–530 cm, 11.2–15 ka) and unit 3 (530–588 cm, 15.0–16.7 ka). These sediments were transported by local westerly winds (units 1 and 3) and fluvial processes (unit 2). Based on major element compositions and geological setting of adjacent areas, provenance of unit 1 sediments was interpreted to be the Lake terrane, and that of unit 2 to be the Idermeg terrane. Unit 3 sediments were derived from the Gobi Altai terrane. The records of total organic carbon, C/N ratio and weathering intensity suggest that paleoclimate in the source area of Lake Ulaan sediment was most humid during the Early Holocene, humid during the mid‐Holocene and dry in the Late Holocene. The decrease of humidity through the Holocene is a typical characteristic of the East Asian monsoon region. Comparison with lacustrine records of other Mongolia regions suggests that the northern boundary of East Asian summer‐monsoon influence could have been located further north than previously assumed. Copyright © 2013 John Wiley & Sons, Ltd.
Studies on Biology, Morphometrics and Substrate Preference of the Burrowing Cockroach Pycnoscelus surinamensis (L.)

Biology of the burrowing cockroach Pycnoscelus surinamensis (L.) revealed that there are four instars and took 134.8±4.94 days to complete lifecycle. Morphometric studies showed increase in antennal body length, head width, pronotum length and width from first to fourth instar with peak at adult and other developmental stages well fit into Brooks-Dyar rule. All body parameters showed hypoallometry except pronotum length which showed hyperallometry. In substrate preference studies, the survival was lowest for the treatment without substrate and against the treatments with substrates like leaf litter, cocopeat and vermiculite. The mean number of offspring produced and survived was found to be lower in the treatments without substrate and with leaf litter against the treatments with cocopeat and vermiculite.
Knowledge Of Families Toward Type 1 Diabetes Among Children In AL-Diwaniyah City, Iraq: Cross-Sectional Study –College of Medicine/ University Of AL-Qadisiyah

Background: Type 1 diabetes is one of the most common chronic diseases in childhood, that is considered a challenge for parents especially when the child is not developmentally able to manage the disease independently. Since optimal glycemic control is required to prevent acute and long-term diabetes-related complications and enhance school performance, the importance of involving adults in the child diabetes management is essential. Aim of the study: The current study aimed to evaluate the knowledge, regarding children with T1DM among families living in Diwaniyah city. Subjects and Method: A cross sectional study conducted in Al Diwaniyah governate, Iraq on a sample of 400 caregivers of type 1 diabetes mellitus diagnosed children for a period of three months. Structured questionnaires were used for Knowledge. Chi -square test was applied to find the significant association between qualitative variables. Independent t test and one way ANOVA were applied to illustrate a significant difference between quantitative variable. In all Statistical analyses, a p value equal or below 5% was considered significant. Results: Majority of caregivers; 192 (48%), were in their forties and married. Mothers 239 (59.8%) were the main caregivers, more than half of the studied sample 237(59.3%) had university or institute educational attainment. The average score for knowledge was 9.39±2.9 scores ranging from 0-12 score. Poor knowledge was found among 64 (16%) of caregivers, while 42(10.5%) and 294(73.5%) scored moderate and good knowledge respectively. Education and urban residency were significantly associated with good knowledge. Lower HbA1C level was seen associated with good diabetes knowledge. Conclusion: Although good knowledge were reported. Such discrepancy requires an increase in public awareness about the T1DM. Using modern technology to disseminate the correct information to caregivers.
Hyperspectral imagery for mapping intertidal vegetation at Roberts Bank tidal flats, British Columbia, Canada

This study assesses the effectiveness of hyperspectral airborne imagery to map the intertidal vegetation at Roberts Bank, a large salt marsh and tidal flat complex in the Fraser River delta, British Columbia, Canada. This ecosystem is an important habitat for migratory and resident birds and fish and is part of the largest single salmon-producing stream in the world, the Fraser River. Imagery acquired by the compact airborne spectrographic imager (CASI) was radiometrically and geometrically corrected and mosaicked. A simple maximum likelihood classifier was used to classify intertidal vegetation cover. Training and test sites were collected using field observations and oblique aerial photographs. Seven vegetation-substrate classes were accurately (92.3%) classified, ranging from muddy sediments in the regularly inundated tidal flat and low marsh areas, to higher marsh communities of cattails, grasses, sedges, and rushes. This study showed that both the hyperspectral and hyperspatial characteristics of the CASI imagery were important for achieving high separability among the classes due to reduced spectral mixing of different substrates at the subpixel scale when compared with simulated Landsat and Ikonos imagery.
Modeling detailed sedimentary 210Pb and fallout 239,240Pu profiles to allow episodic events: An application in Chesapeake Bay

Dependable sediment chronologies are essential to the interpretation of the sedimentary record of past environmental change. In the present article, we use high‐resolution chemical and radiochemical data as the basis for a numerical simulation of sediment accumulation, bioturbation, and episodic deposition or erosion in a dynamic estuary. We simulate episodic events by employing a time dependent sedimentation rate that we solve by finding a set of model parameters that describes depth profiles of both excess 210Pb and fallout 239,240Pu. We apply the model to depth distributions of these tracer nuclides in cores from upper‐, mid‐ and lower‐Bay sites in Chesapeake Bay. At the upper‐Bay site, combining chemical and radiochemical data permits us to recognize and to quantify the sediment deposition due to tropical storm Agnes (1972). At the lower‐Bay site, we demonstrate nonsteady sedimentation and propose plausible scenarios to account for it. Given adequate data, our model can provide information that is not available from steady‐state models.
Keeping Up with the Lunar Meteorites

At this writing, we are aware of 104 lunar meteorite stones, 97 of which have names that have been accepted by the Nomenclature Committee of the Meteoritical Society (2 provisionally) and 7 without accepted names that have nonetheless been described in the literature [1] or that we have recently analyzed and know to be of lunar origin (N=6). At least 8 other alleged lunar meteorite stones are in the hands of reputable dealers and collectors. Ignoring the latter, the known lunar meteorite stones represent as many 46 meteorites and probably not less than about 35. We have obtained compositional data by INAA for 192 subsamples of 31 lunar meteorite stones since our last reports here [2–7]. Some of the data are reported elsewhere [8–14]. Sc (μg/g) 40 50 60 70 80 90 100 110 120 N a 2 O ( % )
Optimal ensemble size of ensemble Kalman filter in sequential soil moisture data assimilation

The ensemble Kalman filter (EnKF) has been extensively applied in sequential soil moisture data assimilation to improve the land surface model performance and in turn weather forecast capability. Usually, the ensemble size of EnKF is determined with limited sensitivity experiments. Thus, the optimal ensemble size may have never been reached. In this work, based on a series of mathematical derivations, we demonstrate that the maximum efficiency of the EnKF for assimilating observations into the models could be reached when the ensemble size is set to 12. Simulation experiments are designed in this study under ensemble size cases 2, 5, 12, 30, 50, 100, and 300 to support the mathematical derivations. All the simulations are conducted from 1 June to 30 September 2012 over southeast USA (from −90°W, 30°N to −80°W, 40°N) at 25 km resolution. We found that the simulations are perfectly consistent with the mathematical derivation. This optical ensemble size may have theoretical implications on the implementation of EnKF in other sequential data assimilation problems.
Efficacy of Insulin Titration Driven by SMS in Improving Glycemic Control in People with Type 2 Diabetes

Aim: To evaluate the efficacy of the self-management of insulin titration based on information received by the Short Message Service (SMS). Methods: A case-control study including 59 subjects in each arm with 16 weeks of follow-up was performed. The inclusion criteria were: (1) Subjects with type 2 diabetes (T2D) under basal insulin treatment; (2) Suboptimal glycemic control: HbA1c ≥ 7.5% and fasting capillary blood glucose (FCBG) > 140 mg/dL (>3 times per week). Subjects were invited to use an insulin titration service based on SMS feedback aimed at optimizing glycemic control depending on fasting blood glucose levels. Psychological aspects were evaluated in the interventional group by means of validated questionnaires (DDS, HADS and SF-12). Results: The intervention group achieved a lower mean FCBG (126 mg/dL ± 34 vs. 149 mg/dL ± 46, p = 0.001) and lower HbA1c (7.5% ± 1.3 vs. 7.9% ± 0.9, p = 0.021) than the control group. In addition, the intervention group showed a significant improvement in psychological aspects related to Emotional Burden (p = 0.031), Regimen Distress (p < 0.001), Depression (p = 0.049) and Mental Health (p < 0.01). Conclusions: The SMS-guided titration was effective in terms of improving glucometric parameters in comparison with the standard of care and improved significant psychological aspects—mainly, the stress associated with insulin treatment
Radiation qualification and optical performance of the InGaAs type imaging sensor for the vSWIR spectral range in the VEM instrument on the VERITAS mission

The Venus Emissivity Mapper (VEM) as part of NASAs Venus Emissivity, Radio science, InSAR, Topography, And Spectroscopy mission (VERITAS) is designed for mapping the surface of Venus within dedicated atmospheric spectral windows. The instrument will provide global coverage for detection of thermal emissions like volcanic activity, surface rock composition, water abundance and cloud formation as well as dynamics by observing 15 narrow filter bands in the near infrared to short wavelength infrared (NIR, SWIR) range of 862 nm to 1510 nm. An almost identical instrument will be part of ESAs EnVision mission to Venus, the VenSpec-M in the Venus Spectroscopy Suite (VenSpec). The utilized photodetector is an InGaAs type imaging sensor with integrated thermoelectric (TE) cooling. It comprises a 640x512 pixel array with 20 μm pixel pitch. Following the mission requirements we irradiated the detector with a set of ions of various stopping powers and range distributions from lower energy Argon (Ar) to higher energy Xenon (Xe). Therefore, exploiting the mentioned ions and proper tilt angles during irradiation, our data covers a Linear Energy Transfer (LET) range of 7 to 75 MeVcm2/mg which fulfills NASA/JPL led space qualification standards (up to 75 MeVcm2/mg) as well as ESA space qualification standards (up to 60 MeVcm2/mg) for heavy-ion irradiation. Our electrical setup consists of a dedicated over-current protection detecting high-current states occurring during irradiation steps and immediate power cycling to prevent physical damage of the device. From the event rates seen during the test we calculated the specific cross-sections and therefore can estimate the expected event rates at Venus during the mission. The detector showed saturated cross-sections below 1E-3 cm2 at 10°C with acceptable event rates for the highest LETs and our applications.