One of the key events in cancer development is the ability of tumor cells to overcome nutrient deprivation and hypoxia. Among proteins performing metabolic adaptation to the various cellular nutrient conditions, liver kinase B 1 (LKB1) and its main downstream target adenosine monophosphate (AMP)-activated protein kinase α (AMPKα) are important sensors of energy requirements within the cell. Caffeic Acid Phenethyl Ester NF-κB inhibitor Although LKB1 was originally described as a tumor suppressor, given its role in metabolism, it potentially acts as a double-edged sword. AMPKα, a master regulator of cell energy demands, is activated when ATP level drops under a certain threshold, responding accordingly through its downstream targets. Twelve downstream kinase targets of LKB1 have been described as AMPKα-like proteins. This group is comprised of novel (nua) kinase family (NUAK) kinases (NUAK1 and 2) linked to cell cycle progression and ultraviolet (UV)-damage; microtubule affinity regulating kinases (MARKs) (MARK1, MARK2, MARK3, and MARK4) that are involved in cell polarity; salt inducible kinases (SIK) (SIK1, SIK2, also known as Qin-induced kinase or QIK and SIK3) that are implicated in cell metabolism and adipose tissue development and mitotic regulation; maternal embryonic leuzine zipper kinase (MELK) that regulate oocyte maturation; and finally brain selective kinases (BRSKs) (BRSK1 and 2), which have been mainly characterized in the brain due to their role in neuronal polarization. Thus, many efforts have been made in order to harness LKB1 kinase and its downstream targets as a possible therapeutic hub in tumor development and propagation. In this review, we describe LKB1 and its downstream target AMPK summarize major functions of various AMPK-like proteins, while focusing on biological functions of BRSK1 and 2 in different models.The majority of homicides in the world are caused by firearms and a good understanding of gunshot wounds is important for the forensic pathologist. We have analyzed all 315 homicides by gunshots in Denmark during 1992-2016 with focus on information relevant to forensic pathologists. Of the 1417 homicides in Denmark in 1992-2016, 315 (22.2%) had gunshot trauma as the primary homicide method. During 1992-2016, there has been a significant decrease in the number of gunshot homicides overall, of homicides committed with hunting weapons, and of domestic gunshot homicides. Most victims (70.5%) and offenders (93.7% of homicides with known offenders) were males. Male victims were significantly younger than female victims. Most victims were killed with handguns (43.8%) or shotguns (41.0%). Compared to all other weapons, the victims killed with shotguns had fewer entry wounds, a higher New Injury Severity Score (NISS), and a higher proportion of contact/close-range entry wounds. The head (58.1%) and thorax (46.7%) were often injured, with injuries to the head being more common in contact/close-range entry wounds. The results show that gunshot injuries in homicides are different from suicides and accidents and clearly are affected by the homicide type, the sex of the victim, and the weapon used and that these entities are intertwined. Our findings provide an evidence-based foundation for use in death investigations and for policy development in the area of interpersonal violence.Age estimation is an important challenge in many fields, including immigrant identification, legal requirements, and clinical treatments. Deep learning techniques have been applied for age estimation recently but lacking performance comparison between manual and machine learning methods based on a large sample of dental orthopantomograms (OPGs). In total, we collected 10,257 orthopantomograms for the study. We derived logistic regression linear models for each legal age threshold (14, 16, and 18 years old) for manual method and developed the end-to-end convolutional neural network (CNN) which classified the dental age directly to compare with the manual method. Both methods are based on left mandibular eight permanent teeth or the third molar separately. Our results show that compared with the manual methods (92.5%, 91.3%, and 91.8% for age thresholds of 14, 16, and 18, respectively), the end-to-end CNN models perform better (95.9%, 95.4%, and 92.3% for age thresholds of 14, 16, and 18, respectively). This work proves that CNN models can surpass humans in age classification, and the features extracted by machines may be different from that defined by human.Arginine (R)-rich peptides constitute the most relevant class of cell-penetrating peptides and other membrane-active peptides that can translocate across the cell membrane or generate defects in lipid bilayers such as water-filled pores. The mode of action of R-rich peptides remains a topic of controversy, mainly because a quantitative and energetic understanding of arginine effects on membrane stability is lacking. Here, we explore the ability of several oligo-arginines R[Formula see text] and of an arginine side chain mimic R[Formula see text] to induce pore formation in lipid bilayers employing MD simulations, free-energy calculations, breakthrough force spectroscopy and leakage assays. Our experiments reveal that R[Formula see text] but not R[Formula see text] reduces the line tension of a membrane with anionic lipids. While R[Formula see text] peptides form a layer on top of a partly negatively charged lipid bilayer, R[Formula see text] leads to its disintegration. Complementary, our simulations show R[Formula see text] causes membrane thinning and area per lipid increase beside lowering the pore nucleation free energy. Model polyarginine R[Formula see text] similarly promoted pore formation in simulations, but without overall bilayer destabilization. We conclude that while the guanidine moiety is intrinsically membrane-disruptive, poly-arginines favor pore formation in negatively charged membranes via a different mechanism. Pore formation by R-rich peptides seems to be counteracted by lipids with PC headgroups. We found that long R[Formula see text] and R[Formula see text] but not short R[Formula see text] reduce the free energy of nucleating a pore. In short R[Formula see text], the substantial effect of the charged termini prevent their membrane activity, rationalizing why only longer [Formula see text] are membrane-active.