Campus Safety: Assessing and Managing Threats

Since the shootings at Virginia Tech, academic institutions and police departments have dedicated substantial resources to alleviating concerns regarding campus safety. The incident in Blacksburg and the similar tragedy at Northern Illinois University have brought renewed attention to the prevention of violence at colleges and universities. Campus professionals must assess the risk posed by known individuals, as well as by anonymous writers of threatening communications. The authors offer threat assessment and management strategies to address the increased demands faced by campus law enforcement, mental health, and administration officials who assess and manage threats, perhaps several simultaneously

The effects of signal transducer and activator of transcription three mutations on human platelets

Involvement of signal transducer and activator of transcription 3 (STAT3) in inflammation is well known. Recently, a role for STAT3 in platelet activation and platelet production has been suggested. Platelets exhibit important immune functions and engagement of STAT3 in platelet physiology may link inflammation and hemostasis. This study investigated the effects of STAT3 loss-of-function mutations and single nucleotide polymorphisms (SNPs) in STAT3 on glycoprotein VI (GPVI)-mediated platelet activation and platelet numbers in humans. Two cohorts were studied. The first cohort concerned patients with STAT3 loss-of-function mutations. Platelet numbers were investigated in eight patients and GPVI-mediated platelet activation was functionally tested in four patients. Additional experiments were performed to investigate underlying mechanisms. The second cohort concerned 334 healthy volunteers and investigated the consequences of SNPs in STAT3 on GPVI-mediated platelet activation and platelet numbers. Platelet activation was lower in STAT3 loss-of-function patients at baseline and after stimulation of the GPVI receptor, reflected by decreased P-selectin expression. This was independent of gene transcription. Blockade of the adenosine di-phosphate (ADP) pathway resulted in a further decrease of P-selectin expression, particularly in STAT3 loss-of-function patients. In contrast, the SNPs in STAT3 did not influence GPVI-mediated platelet activation. Also, platelet numbers were not affected by STAT3 loss-of-function mutations, nor was there an association with the SNPs. In conclusion, STAT3 signaling does not seem to play a major role in thrombopoiesis. We confirm that STAT3 is involved in GPVI-mediated platelet activation in humans, independent of gene transcription. GPVI-mediated platelet activation is highly dependent on secondary ADP release. Our findings suggest that STAT3 modulation may affect inflammation, hemostasis, and their interaction.</p

Family Podocnemididae.

237 p. : ill. ; 26 cm. "Issued April 29, 2011."The family Podocnemididae consists of 20 genera and 30 species considered here as valid and diagnosable by cranial characters. Three of these genera and eight species persist into the Recent fauna, barely reflecting the evolutionary diversity and distribution of the group. The family extends from the late Cretaceous to the Recent and occurs in North and South America, Europe, Asia, and Africa. A phylogenetic analysis utilizes 31 podocnemidid taxa (30 named and one unnamed; a total of 37 taxa analyzed includes outgroups) in the Podocnemididae that are analyzed using PAUP. The resulting consensus of nine equally parsimonious cladograms is the basis for a new classification of the family. The family Podocnemididae is reconfirmed as monophyletic, using the unique possession of a cavum pterygoidei formed by the basisphenoid, pterygoid, prootic, and quadrate, underlain by the pterygoid and basisphenoid, among other characters. Much of our resolution agrees with that of França and Langer (2006), which can be modified and restated as follows: (Bauruemys (vilavilensis (Podocnemis (Peltocephalus, Erymnochelys)))). The two clades proposed by Broin (1991) and Lapparent de Broin (2000b, 2001, 2003a, 2003b), designated by her as the "subfamily Podocnemidinae" and the "subfamily Erymnochelinae," are inconsistent with our analysis. In our analysis the "Podocnemidinae" (sensu Broin, 1991) is paraphyletic, and the "Erymnochelinae" (sensu Broin, 1991) could be made monophyletic, with the important addition of Peltocephalus (placed in the "Podocnemidinae" by Broin). We add a number of new taxa to the basal Podocnemididae and to the broad-jawed subtribe Stereogenyina. Within the family Podocnemididae Cope, 1868, the sister taxon to all other podocnemidids and recognized as the subfamily Bauruemydinae, new, is Bauruemys elegans (Suárez, 1969a), known from associated skulls and shells. All other podocnemidids, the redefined subfamily Podocnemidinae Cope, 1868, are united by a slight to absent temporal emargination, a completely closed foramen jugulare posterius, and saddle-shaped cervical centra (modified as a separate state in Erymnochelys). A basal group of Cretaceous-Paleocene podocnemidids that are the sister group to all remaining podocnemidids, here termed the infrafamily Peiropemydodda, consisting of two taxa from the late Cretaceous of Brazil, Peiropemys mezzalirai, n. gen. et sp., and Pricemys caiera, n. gen. et sp., and Lapparentemys vilavilensis (Broin, 1971), n. gen., from the Paleocene of Bolivia. The resolution of the basal members of the family is: (Bauruemys (Pricemys (Lapparentemys, Peiropemys)) (Infrafamily Podocnemidodda)). The remaining podocnemidids form the infrafamily Podocnemidodda Cope, 1868, new rank, and is characterized by the possession of a cheek emargination that does not reach above the level of the orbit, the medial expansion of the triturating surfaces with a median maxillary ridge present, and the presence of accessory ridges on the triturating surfaces. This group contains the living podocnemidids and a series of extinct forms, including the marine broad-jawed taxa. Within the Podocnemidodda, the genus Podocnemis is the sister group to all the remaining taxa, which is the magnatribe Erymnochelydand. When only the living fauna is considered our results show Podocnemis as the sister taxon to Erymnochelys plus Peltocephalus, in common with Williams (1954c), Franc¸a and Langer (2006), Meylan et al. (2009), and Cadena et al. (2010). With the fossil taxa present, the Erymnochelydand is united only by the small to absent cheek emargination. However, some of the fossil taxa (i.e., Caninemys, Dacquemys), are not known for a number of characters, and, if the analysis is reduced to include only the living species, Erymnochelys and Peltocephalus are united by a greater number of characters: cavum pterygoidei with enlarged anterior opening, so that the foramen cavernosum enters the roof of the cavum pterygoidei, orbits facing anterolaterally, jugal-quadrate contact present, cheek emargination slight to absent, horizontal occipital shelf absent, premaxillae reach apertura narium interna (also in some Podocnemis), supraoccipital roof exposure slight or absent, chorda tympani enclosed in processus retroarticularis, neural series extends to costal six, and axillary musk duct not in bridge. When one considers just the Recent genera, none of the published molecular results reproduce the Gaffney and Meylan (1988) and Lapparent de Broin (2000b) resolution of (Erymnochelys (Podocnemis, Peltocephalus)); rather these publications show a preference for the (Peltocephalus (Podocnemis, Erymnochelys)) arrangement, while we, in agreement with Franc¸a and Langer (2006) and the earlier version of the present data set, Meylan et al. (2009), place our marbles with the third alternative, (Podocnemis (Peltocephalus, Erymnochelys)). This latter hypothesis has a number of characters favoring its resolution, even when fossils are excluded. One of the more compelling ones is the large cavum pterygoidei with an enlarged anterior opening and the foramen cavernosum containing the lateral head vein, entering the roof of the cavum pterygoidei. Within the magnatribe Erymnochelydand are the following taxa: Caninemys, Dacquemys, unnamed genus UCMP 42008, Albertwoodemys, Turkanemys, Peltocephalus, Erymnochelys, Neochelys, Papoulemys, and the members of the tribe Stereogenyini (see below). The resolution of Caninemys within the Erymnochelydand is not strongly supported; in only one step it becomes a multichotomy with Podocnemis and the infrafamily Peiropemydodda. Neochelys, Papoulemys (possibly a synonym of Neochelys), and Dacquemys, however, are strongly supported as part of the magnatribe Erymnochelydand, as proposed earlier (Broin, 1991; Lapparent de Broin, 2000b, 2001, 2003a, 2003b). A new shell-based taxon, Albertwoodemys testudinum, n. gen. et sp., and an unnamed skull and shell, UCMP 42008, are united by a high-domed shell with thick lateral ridges along the plastron and the absence/fusion of the pectoral scales. The skull of UCMP 42008 agrees with that in Dacquemys in having large parietals and a supraoccipital covering the posterior margin. Lacking a skull, Albertwoodemys is not entered into the data set, but the skull-shell specimen of the closely related UCMP 42008 is in the analysis. New skull material identifiable as Neochelys has been discovered associated with shells of ‘‘Podocnemis’’ fajumensis Andrews, 1903, resulting in the new combination Neochelys fajumensis (Andrews, 1903). Neochelys has the Erymnochelydand synapomorphy of a large cavum pterygoidei with an enlarged anterior opening and the foramen cavernosum entering the roof of the cavum pterygoidei, as in Peltocephalus and Erymnochelys. The European Neochelys species are Eocene and the African Fayum species is Early Oligocene, extending both spatial and temporal ranges of the genus. The tribe Stereogenyini has a dorsal process of the palatine that reaches the frontal in the septum orbitotemporale, the fossa precolumellaris is absent, and both foramina nervi hypoglossi are combined and recessed in a short canal that opens on the occipital surface. Within the tribe Stereogenyini, Mogharemys blanckenhorni Dacque´ (1912), n. gen., is the sister taxon to the welldefined subtribe Stereogenyina. Two groups are recognized within the subtribe Stereogenyina. The infratribe Bairdemydita contains Bairdemys Gaffney and Wood, Latentemys plowdeni, n. gen. et sp., Cordichelys antiqua (Andrews, 1903), n. gen. The infratribe Stereogenyita contains Brontochelys gaffneyi (Wood, 1970), n. gen., Lemurchelys diasphax, n. gen. et sp., Shweboemys Swinton, 1939, and Stereogenys Andrews, 1901. The subtribe Stereogenyina is strongly supported by a secondary palate with a median cleft, unique among turtles, as well as other characters. While the other Podocnemididae were apparently freshwater species, there is evidence that many or all of the subtribe Stereogenyina were marine or near-shore marine. Compared with a group such as the Bothremydidae, we see in the evolution of the Podocnemididae, a relatively conservative series of South American paraphyletic taxa with an unusually persistent cranial as well as shell morphology, beginning in the Late Cretaceous with Bauruemys, Peiropemys, and Pricemys, and continuing with the Paleocene Lapparentemys, culminating in the Recent Podocnemis. A monophyletic Tertiary group with more geographic, taxonomic, and morphologic diversity, the magnatribe Erymnochelydand, contains African, European, Asian, and South American taxa, as well as a radiation of marine, broad-jawed species in the mid-Tertiary. The living remnants of the Erymnochelydand are the South American Peltocephalus and the African Erymnochelys, close relatives despite their current geographic separation

Cerebellar repetitive transcranial magnetic stimulation restores pharyngeal brain activity and swallowing behaviour after disruption by a cortical virtual lesion

Repetitive transcranial magnetic stimulation (rTMS) can alter neuronal activity within the brain with therapeutic potential. Low frequency stimulation to the ‘dominant’ cortical swallowing projection induces a ‘virtual‐lesion’ transiently suppressing cortical excitability and disrupting swallowing behaviour. Here, we compared the ability of ipsi‐lesional, contra‐lesional and sham cerebellar rTMS to reverse the effects of a ‘virtual‐lesion’ in health. Two groups of healthy participants (n = 15/group) were intubated with pharyngeal catheters. Baseline pharyngeal motor evoked potentials (PMEPs) and swallowing performance (reaction task) were measured. Participants received 10 min of 1 Hz rTMS to the pharyngeal motor cortex which elicited the largest PMEPs to suppress cortical activity and disrupt swallowing behaviour. Over six visits, participants were randomized to receive 250 pulses of 10 Hz cerebellar rTMS to the ipsi‐lesional side, contra‐lesional side or sham while assessing PMEP amplitude or swallowing performance for an hour afterwards. Compared to sham, active cerebellar rTMS, whether administered ipsi‐lesionally (P = 0.011) or contra‐lesionally (P = 0.005), reversed the inhibitory effects of the cortical ‘virtual‐lesion’ on PMEPs and swallowing accuracy (ipsi‐lesional, P < 0.001, contra‐lesional, P < 0.001). Cerebellar rTMS was able to reverse the disruptive effects of a ‘virtual lesion’. These findings provide evidence for developing cerebellar rTMS into a treatment for post‐stroke dysphagia

The Maunakea Spectroscopic Explorer Book 2018

(Abridged) This is the Maunakea Spectroscopic Explorer 2018 book. It is intended as a concise reference guide to all aspects of the scientific and technical design of MSE, for the international astronomy and engineering communities, and related agencies. The current version is a status report of MSE's science goals and their practical implementation, following the System Conceptual Design Review, held in January 2018. MSE is a planned 10-m class, wide-field, optical and near-infrared facility, designed to enable transformative science, while filling a critical missing gap in the emerging international network of large-scale astronomical facilities. MSE is completely dedicated to multi-object spectroscopy of samples of between thousands and millions of astrophysical objects. It will lead the world in this arena, due to its unique design capabilities: it will boast a large (11.25 m) aperture and wide (1.52 sq. degree) field of view; it will have the capabilities to observe at a wide range of spectral resolutions, from R2500 to R40,000, with massive multiplexing (4332 spectra per exposure, with all spectral resolutions available at all times), and an on-target observing efficiency of more than 80%. MSE will unveil the composition and dynamics of the faint Universe and is designed to excel at precision studies of faint astrophysical phenomena. It will also provide critical follow-up for multi-wavelength imaging surveys, such as those of the Large Synoptic Survey Telescope, Gaia, Euclid, the Wide Field Infrared Survey Telescope, the Square Kilometre Array, and the Next Generation Very Large Array.Comment: 5 chapters, 160 pages, 107 figure

A major QTL controlling apple skin russeting maps on the linkage group 12 of 'Renetta Grigia di Torriana'

Background: Russeting is a disorder developed by apple fruits that consists of cuticle cracking followed by the replacement of the epidermis by a corky layer that protects the fruit surface from water loss and pathogens. Although influenced by many environmental conditions and orchard management practices, russeting is under genetic control. The difficulty in classifying offspring and consequent variable segregation ratios have led several authors to conclude that more than one genetic determinant could be involved, although some evidence favours a major gene (Ru). Results: In this study we report the mapping of a major genetic russeting determinant on linkage group 12 of apple as inferred from the phenotypic observation in a segregating progeny derived from 'Renetta Grigia di Torriana', the construction of a 20 K Illumina SNP chip based genetic map, and QTL analysis. Recombination analysis in two mapping populations restricted the region of interest to approximately 400 Kb. Of the 58 genes predicted from the Golden Delicious sequence, a putative ABCG family transporter has been identified. Within a small set of russeted cultivars tested with markers of the region, only six showed the same haplotype of 'Renetta Grigia di Torriana'. Conclusions: A major determinant (Ru_RGT) for russeting development putatively involved in cuticle organization is proposed as a candidate for controlling the trait. SNP and SSR markers tightly co-segregating with the Ru_RGT locus may assist the breeder selection. The observed segregations and the analysis of the 'Renetta Grigia di Torriana' haplotypic region in a panel of russeted and non-russeted cultivars may suggest the presence of other determinants for russeting in apple

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment