A Mathematical Approach to the Study of the United States Code

The United States Code (Code) is a document containing over 22 million words that represents a large and important source of Federal statutory law. Scholars and policy advocates often discuss the direction and magnitude of changes in various aspects of the Code. However, few have mathematically formalized the notions behind these discussions or directly measured the resulting representations. This paper addresses the current state of the literature in two ways. First, we formalize a representation of the United States Code as the union of a hierarchical network and a citation network over vertices containing the language of the Code. This representation reflects the fact that the Code is a hierarchically organized document containing language and explicit citations between provisions. Second, we use this formalization to measure aspects of the Code as codified in October 2008, November 2009, and March 2010. These measurements allow for a characterization of the actual changes in the Code over time. Our findings indicate that in the recent past, the Code has grown in its amount of structure, interdependence, and language.Comment: 5 pages, 6 figures, 2 tables

Learning Theory Expertise in the Design of Learning Spaces: Who Needs a Seat at the Table?

This study highlights the impact of including stakeholders with expertise in learning theory in a learning space design process. We present the decision-making process during the design of the Krause Innovation Studio on the campus of the Pennsylvania State University to draw a distinction between the architect and faculty member’s decision-making process. Often, the architect relied on guiding principles such as flexibility, while the faculty member drew from learning theory such as the sociocultural theory of learning (Vygotsky, 1978). This study demonstrates the value of learning theory expertise and includes suggestions and possible implications for future designs of learning spaces

Forming and Sustaining a Learning Community and Developing Implicit Collective Goals in an Open Future Learning Space

This study investigates the role of space, material, and affect in undergraduate and graduate students’ lived experiences within an open Future Learning Space (FLS) and speaks to the call for research on learning communities in learning spaces, as described in Hod, Bielaczyc, and Ben-Zvi (2018). The methodological approach consists of semi-structured phenomenological interviews with thirteen users of the FLS and thematic analysis to uncover themes. Findings suggest the FLS was able to: (1) bring together individuals by producing individual and shared affective responses; (2) hold community together and inform perceptions; and (3) move the community together and shape practices. This study indicates that open FLSs are complex systems constructed by users and can meet some of the criteria for a learning community (LC), especially if we broaden the definitions to take into account implicit versions of an LC

Primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphomas: reappraisal of a provisional entity in the 2016 WHO classification of cutaneous lymphomas.

Primary cutaneous CD8-positive aggressive epidermotropic T-cell lymphoma is a rare and poorly characterized variant of cutaneous lymphoma still considered a provisional entity in the latest 2016 World Health Organization Classification of Cutaneous lymphomas. We sought to better characterize and provide diagnostic and therapeutic guidance of this rare cutaneous lymphoma. Thirty-four patients with a median age of 77 years (range 19-89 years) presented primarily with extensive annular necrotic plaques or tumor lesions with frequent mucous membrane involvement. The 5-year survival was 32% with a median survival of 12 months. A subset of 17 patients had a prodrome of chronic patches prior to the development of aggressive ulcerative lesions. We identified cases with lack of CD8 or αβ T-cell receptor expression yet with similar clinical and pathological presentation. Allogeneic stem cell transplantation provided partial or complete remissions in 5/6 patients. We recommend the term primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphoma as this more broad designation better describes this clinical-pathologic presentation, which allows the inclusion of cases with CD8 negative and/or αβ/γδ T-cell receptor chain double-positive or double-negative expression. We have identified early skin signs of chronic patch/plaque lesions that are often misdiagnosed as eczema, psoriasis, or mycosis fungoides. Our experience confirms the poor prognosis of this entity and highlights the inefficacy of our standard therapies with the exception of allogeneic stem cell transplantation in selected cases

Assessing sampling of the fossil record in a geographically and stratigraphically constrained dataset: the Chalk Group of Hampshire, southern UK

Taphonomic, geological and sampling processes have been cited as biasing richness measurements in the fossil record, and sampling proxies have been widely used to assess this. However, the link between sampling and taxonomic richness is poorly understood, and there has been much debate over the equivalence and relevance of proxies. We approach this question by combining both historical and novel data: a historical fossil occurrence dataset with uniquely high spatial resolution from the Upper Cretaceous Chalk Group of Hampshire, UK, and a newly-compiled 3D geological model which maps subsurface extent. The geological model provides rock volumes, and these are compared with exposure and outcrop area, sampling proxies that have often been conflated in previous studies. The extent to which exposure area (true rock availability) has changed over research time is also tested. We find a trend of low Cenomanian to high Turonian to Campanian raw richness, which correlates with, and is possibly driven by the number of specimens found. After sampling standardisation, an unexpected mid-Turonian peak diversity is recovered, and sampling-standardised genus richness is best predicted by rock volume, suggesting a species-area (or, a “genus-area”) effect. Additionally, total exposure area has changed over time, but relative exposure remains the same

Pathogenic Intestinal Bacteria Enhance Prostate Cancer Development via Systemic Activation of Immune Cells in Mice

A role for microbes has been suspected in prostate cancer but difficult to confirm in human patients. We show here that a gastrointestinal (GI) tract bacterial infection is sufficient to enhance prostate intraepithelial neoplasia (PIN) and microinvasive carcinoma in a mouse model. We found that animals with a genetic predilection for dysregulation of wnt signaling, Apc[superscript Min/+] mutant mice, were significantly susceptible to prostate cancer in an inflammation-dependent manner following infection with Helicobacter hepaticus. Further, early neoplasia observed in infected Apc[superscript Min/+] mice was transmissible to uninfected mice by intraperitoneal injection of mesenteric lymph node (MLN) cells alone from H. hepaticus-infected mutant mice. Transmissibility of neoplasia was preventable by prior neutralization of inflammation using anti-TNF-α antibody in infected MLN donor mice. Taken together, these data confirm that systemic inflammation triggered by GI tract bacteria plays a pivotal role in tumorigenesis of the prostate gland.RO1CA108854National Institute of Environmental Health Sciences (Massachusetts Institute of Technology. Center for Environmental Health Sciences Pilot Project Award P30-ES002109

Increased production of IL-4 and IL-12p40 from bronchoalveolar lavage cells are biomarkers of Mycobacterium tuberculosis in the sputum

BACKGROUND: Tuberculosis (TB) causes 1.45 million deaths annually world wide, the majority of which occur in the developing world. Active TB disease represents immune failure to control latent infection from airborne spread. Acid-fast bacillus (AFB) seen on sputum smear is a biomarker for contagiousness. METHODS: We enrolled 73 tuberculosis patients with extensive infiltrates into a research study using bronchoalveolar lavage (BAL) to sample lung immune cells and assay BAL cell cytokine production. All patients had sputum culture demonstrating Mycobacterium tuberculosis and 59/73 (81%) had AFB identified by microscopy of the sputum. Compared with smear negative patients, smear positive patients at presentation had a higher proportion with smoking history, a higher proportion with temperature >38.5 0 C, higher BAL cells/ml, lower percent lymphocytes in BAL, higher IL-4 and IL-12p40 in BAL cell supernatants. There was no correlation between AFB smear and other BAL or serum cytokines. Increasing IL-4 was associated with BAL PMN and negatively associated with BAL lymphocytes. Each 10-fold increase in BAL IL-4 and IL-12p40 increased the odds of AFB smear positivity by 7.4 and 2.2-fold, respectively, in a multi-variable logistic model. CONCLUSION: Increasing IL-4 and IL-12p40 production by BAL cells are biomarkers for AFB in sputum of patients who present with radiographically advanced TB. They likely reflect less effective immune control of pathways for controlling TB, leading to patients with increased infectiousness

B Cell Depletion in HIV-1 Subtype A Infected Ugandan Adults: Relationship to CD4 T Cell Count, Viral Load and Humoral Immune Responses

To better understand the nature of B cell dysfunctions in subjects infected with HIV-1 subtype A, a rural cohort of 50 treatment-naïve Ugandan patients chronically infected with HIV-1 subtype A was studied, and the relationship between B cell depletion and HIV disease was assessed. B cell absolute counts were found to be significantly lower in HIV-1+ patients, when compared to community matched negative controls (p<0.0001). HIV-1-infected patients displayed variable functional and binding antibody titers that showed no correlation with viral load or CD4+ T cell count. However, B cell absolute counts were found to correlate inversely with neutralizing antibody (NAb) titers against subtype A (p = 0.05) and subtype CRF02_AG (p = 0.02) viruses. A positive correlation was observed between subtype A gp120 binding antibody titers and NAb breadth (p = 0.02) and mean titer against the 10 viruses (p = 0.0002). In addition, HIV-1 subtype A sera showed preferential neutralization of the 5 subtype A or CRF02_AG pseudoviruses, as compared with 5 pseudoviruses from subtypes B, C or D (p<0.001). These data demonstrate that in patients with chronic HIV-1 subtype A infection, significant B cell depletion can be observed, the degree of which does not appear to be associated with a decrease in functional antibodies. These findings also highlight the potential importance of subtype in the specificity of cross-clade neutralization in HIV-1 infection

Identification of Candida glabrata genes involved in pH modulation and modification of the phagosomal environment in macrophages

notes: PMCID: PMC4006850types: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov'tCandida glabrata currently ranks as the second most frequent cause of invasive candidiasis. Our previous work has shown that C. glabrata is adapted to intracellular survival in macrophages and replicates within non-acidified late endosomal-stage phagosomes. In contrast, heat killed yeasts are found in acidified matured phagosomes. In the present study, we aimed at elucidating the processes leading to inhibition of phagosome acidification and maturation. We show that phagosomes containing viable C. glabrata cells do not fuse with pre-labeled lysosomes and possess low phagosomal hydrolase activity. Inhibition of acidification occurs independent of macrophage type (human/murine), differentiation (M1-/M2-type) or activation status (vitamin D3 stimulation). We observed no differential activation of macrophage MAPK or NFκB signaling cascades downstream of pattern recognition receptors after internalization of viable compared to heat killed yeasts, but Syk activation decayed faster in macrophages containing viable yeasts. Thus, delivery of viable yeasts to non-matured phagosomes is likely not triggered by initial recognition events via MAPK or NFκB signaling, but Syk activation may be involved. Although V-ATPase is abundant in C. glabrata phagosomes, the influence of this proton pump on intracellular survival is low since blocking V-ATPase activity with bafilomycin A1 has no influence on fungal viability. Active pH modulation is one possible fungal strategy to change phagosome pH. In fact, C. glabrata is able to alkalinize its extracellular environment, when growing on amino acids as the sole carbon source in vitro. By screening a C. glabrata mutant library we identified genes important for environmental alkalinization that were further tested for their impact on phagosome pH. We found that the lack of fungal mannosyltransferases resulted in severely reduced alkalinization in vitro and in the delivery of C. glabrata to acidified phagosomes. Therefore, protein mannosylation may play a key role in alterations of phagosomal properties caused by C. glabrata.Deutsche ForschungsgemeinschaftNational Institutes for HealthWellcome TrustBBSR