American Indian Transportation Issues in South Dakota

This paper provides an overview of tribal transportation obstacles. My primary focus is on the quality of reservation roads and its relationship to funding and politics. The Indian reservation road system is one of the most underdeveloped transportation networks in the United States. A majority of these roads are dirt and gravel and, therefore, dangerous for traveling. Motor vehicle accidents are the leading cause of death for American Indians and Alaska Natives between ages one and 44 (Hamilton 2003). Because federal funds for tribal transportation fall short of transportation needs, tribes do not have enough money for either road construction materials or road repair and maintenance. As a result, reservation roads are undeveloped and have come under a state of disrepair. Tribal politics are of particular importance in reference to road management. Tribal officials rarely serve terms longer than two or three years. Few officials are reelected and brief terms make efficient management difficult. Compounding the issue is an overall lack of communication between tribal officials and between state, federal, and tribal transportation departments. In addition, one interviewee states Families control tribal government (BIA Highway Engineer). While the needs of the families in governmental positions come first, the needs of tribal members come second. In addition, a BIA employee reports mismanagement of funds, incomplete financial records, corrupt government, and more. The list of tribal transportation problems is a lengthy one, but the list of solutions is brief. Suggested improvements include an open line of communication, hiring and maintaining competent tribal employees, and increased funds. Further research needs to be conducted in this area to investigate effective transportation models. Furthermore, transportation problems negatively affect American Indian employment, health, and education. Little has been researched in this area, and a further investigation needs to be conducted to determine how these areas are affected

CRISPR antiphage defence mediated by the cyclic nucleotide-binding membrane protein Csx23

Biotechnology and Biological Sciences Research Council [BB/T004789/1 to M.F.W., T.M.G.]; European Research Council Advanced Grant [101018608 to M.F.W.]; Engineering and Physical Sciences Research Council [EP/X016455/1 to K.A., B.E.B., M.F.W.]; BBSRC equipment grants [BB/R013780/1, BB/T017740/1 to B.E.B.]. Funding for open access charge: University of St Andrews block grant.CRISPR-Cas provides adaptive immunity in prokaryotes. Type III CRISPR systems detect invading RNA and activate the catalytic Cas10 subunit, which generates a range of nucleotide second messengers to signal infection. These molecules bind and activate a diverse range of effector proteins that provide immunity by degrading viral components and/or by disturbing key aspects of cellular metabolism to slow down viral replication. Here, we focus on the uncharacterised effector Csx23, which is widespread in Vibrio cholerae. Csx23 provides immunity against plasmids and phage when expressed in Escherichia coli along with its cognate type III CRISPR system. The Csx23 protein localises in the membrane using an N-terminal transmembrane α-helical domain and has a cytoplasmic C-terminal domain that binds cyclic tetra-adenylate (cA4), activating its defence function. Structural studies reveal a tetrameric structure with a novel fold that binds cA4 specifically. Using pulse EPR, we demonstrate that cA4 binding to the cytoplasmic domain of Csx23 results in a major perturbation of the transmembrane domain, consistent with the opening of a pore and/or disruption of membrane integrity. This work reveals a new class of cyclic nucleotide binding protein and provides key mechanistic detail on a membrane-associated CRISPR effector.Many anti-viral defence systems generate a cyclic nucleotide signal that activates cellular defences in response to infection. Type III CRISPR systems use a specialised polymerase to make cyclic oligoadenylate (cOA) molecules from ATP. These can bind and activate a range of effector proteins that slow down viral replication. In this study, we focussed on the Csx23 effector from the human pathogen Vibrio cholerae – a trans-membrane protein that binds a cOA molecule, leading to anti-viral immunity. Structural studies revealed a new class of nucleotide recognition domain, where cOA binding is transmitted to changes in the trans-membrane domain, most likely resulting in membrane depolarisation. This study highlights the diversity of mechanisms for anti-viral defence via nucleotide signalling.Peer reviewe

The Grizzly, November 2, 2006

Escape Velocity Dancers Light Up the Stage in the Black Box Theater • Letter to the Editor • Drive to Support the Troops a Success • Ursinus Homecoming 2006: There\u27s No Place Like Home • Blood Drive a Success on Campus • Batteries Included • A Look at Muslim Women in History: Professor Barbara R. von Schlegell Speaks • UC\u27s Opportunity to Support American Troops • Haunting Tales from Main Street • 2008 Preview: Part I • Opinions: Iraq: Should We Stay or Should We Go? • Football Pounds Hopkins on Homecoming • One Win and In for Women\u27s Soccer • Homecoming Victory for Field Hockeyhttps://digitalcommons.ursinus.edu/grizzlynews/1723/thumbnail.jp

The Grizzly, November 30, 2006

Alcohol Awareness on the Front Burner of the Ursinus Campus • Diversity Forum Held for Staff and Students • 2nd Annual Relay for Life Officially Kicked Off at Ursinus • Town Hall Discusses Incidents on Campus • An Oral Examination • UCDC Performs Superbly in Latest Show • People Seeing People: The Artwork of Seward Johnson • Highlights of the Exposure Week Events and Festivities • Opinions: The Meaning of Liberal Arts; Racism in Our World and Home • Ursinus 2006 Division III Field Hockey National Champions! • Swimming to Successhttps://digitalcommons.ursinus.edu/grizzlynews/1726/thumbnail.jp

Development of the Human Fetal Kidney from Mid to Late Gestation in Male and Female Infants

BACKGROUND During normal human kidney development, nephrogenesis (the formation of nephrons) is complete by term birth, with the majority of nephrons formed late in gestation. The aim of this study was to morphologically examine nephrogenesis in fetal human kidneys from 20 to 41weeks of gestation. METHODS Kidney samples were obtained at autopsy from 71 infants that died acutely in utero or within 24h after birth. Using image analysis, nephrogenic zone width, the number of glomerular generations, renal corpuscle cross-sectional area and the cellular composition of glomeruli were examined. Kidneys from female and male infants were analysed separately. FINDINGS The number of glomerular generations formed within the fetal kidneys was directly proportional to gestational age, body weight and kidney weight, with variability between individuals in the ultimate number of generations (8 to 12) and in the timing of the cessation of nephrogenesis (still ongoing at 37weeks gestation in one infant). There was a slight but significant (r2=0.30, P=0.001) increase in renal corpuscle cross-sectional area from mid gestation to term in females, but this was not evident in males. The proportions of podocytes, endothelial and non-epithelial cells within mature glomeruli were stable throughout gestation. INTERPRETATION These findings highlight spatial and temporal variability in nephrogenesis in the developing human kidney, whereas the relative cellular composition of glomeruli does not appear to be influenced by gestational age.This study was supported by funding from the National Health and Medical Research Council (NHMRC) (1011136) of Australia and National Institutes of Health (NIH) USA grant 3U01DK094526-04S1 (PI A P McMahon). Author Danica Ryan was the recipient of the Biomedicine Discovery Scholarship from Monash University and author Megan R. Sutherland was supported by a NHMRC CJ Martin Fellowship

The Grizzly, October 5, 2006

Family Day 2006 Hits Ursinus • Monumental Players in the Black Arts Movement Speak at Ursinus • MSA and Hillel Broke the Fast Together • Free Fitness Class Offered to Ursinus Students • Popping the Pill • Catching Up with Dane Cook • Spotlight on UC Professors: Dr. Bruce Rideout • Abstract Mastery: Exploring the Outdoor Sculpture Collection • Opinions: Forced Suffrage? • Bears Terrorize McDaniel, Ending Nine-Year Streak • Women Split, Men Earn First Conference Pointhttps://digitalcommons.ursinus.edu/grizzlynews/1720/thumbnail.jp

The Grizzly, December 7, 2006

Facing Facebook: Ursinus Administrators Show Students the Dangers of Internet Use • New Berman Exhibit to be Longest Running Show • Ursinus Administration Supports WeCAN\u27s Backing of Workers\u27 Rights • Sounds of Gospel Music Bless the Lenfest Stage • Unraveling the Floy Lewis Bakes Center • What is Rushing? • Health in Ten Questions: Influenza • Opinions: What\u27s Happened to our Movies?; Christmas: A Season of Pretension • Men\u27s Basketball Looks for Three-peat, Women Contenders in Centennial Conferencehttps://digitalcommons.ursinus.edu/grizzlynews/1727/thumbnail.jp

The Grizzly, September 7, 2006

WeCAN Kicks Off the School Year with a Protest for Workers\u27 Rights • Crocodile Hunter Killed by a Stingray • Freshmen Attend First Common Hour • Construction on Campus • Dell Announces Recall • Alternate Energy Sources Needed to Insure Globally-Sound Future • Stopping the Stork: Emergency Contraception • Women, Thou Art Loose: A Concise, Candid Discussion on Sluts, Smuts and Hoes • Opinions: The New Zack\u27s; Dylan Strikes Gold; We Want Water! • Men\u27s Soccer Looking for Breakout Season • Harper and Gibson Carry Bears to Home Opener Victoryhttps://digitalcommons.ursinus.edu/grizzlynews/1716/thumbnail.jp

The Grizzly, September 21, 2006

Curtains Up at Ursinus • New Face in Student Activities • Less Pain at the Pump • WeCAN Action has Impact! • USGA Prepared for New Year • One-Man Show Brings Love to Ursinus • Spotlight on Faculty: Cynthia Port • Computing Services Keeps Campus Up-to-Date • Help Me Help You • Excuse Me, Could You Pass the Love? • Fall Study Abroad Information • Get Paid and Gain Experience Through Internships in Philadelphia • Opinions: Honor Code; What is Patriotism? • Men\u27s Soccer Struggles at Home • Women\u27s Soccer Split Non-Conference Gameshttps://digitalcommons.ursinus.edu/grizzlynews/1718/thumbnail.jp

Twice-daily amprenavir 1200 mg versus amprenavir 600 mg/ritonavir 100 mg, in combination with at least 2 other antiretroviral drugs, in HIV-1-infected patients

BACKGROUND: Low-dose ritonavir (RTV) boosts plasma amprenavir (APV) exposure. Little has been published on the efficacy, tolerability, and safety of APV 600 mg/RTV 100 mg (APV600/RTV) twice daily (BID) compared to APV 1200 mg BID (APV1200). METHODS: ESS40011 was a 24-week, multicenter, open-label, clinical trial in which antiretroviral therapy-naïve and -experienced HIV-1-infected adults were randomized 3:1 to receive either APV600/RTV BID or APV1200 BID, in combination with ≥ 2 non-protease inhibitor antiretroviral drugs. Non-inferiority of the APV600/RTV regimen to the APV1200 regimen was established if the 95% lower confidence limit for the difference in proportion of patients achieving HIV-1 RNA <200 copies/mL at week 24 with APV 600/RTV minus APV1200 was ≥-0.12. Late in the conduct of the trial, patients not yet completing 24 weeks of therapy were given the option of continuing treatment for an additional 24-week period. RESULTS: 211 patients were randomized, 158 to APV600/RTV and 53 to APV1200. At week 24, APV600/RTV was similar to or better than APV1200 (HIV-1 RNA <200 copies/mL in 62% [73/118] vs 53% [20/38] of patients; intent-to-treat: observed analysis). In the APV600/RTV arm, significantly more patients achieved HIV-1 RNA <50 copies/mL (48% [57/118] vs 29% [11/38] with APV1200, P = 0.04), and greater mean reduction from baseline in HIV-1 RNA was observed (-2.21 vs -1.59 log(10 )copies/mL, P = 0.028). The two treatment arms were similar with respect to mean overall change from baseline in CD4+ count, frequency of drug-related grade 1–4 adverse events, and frequency of discontinuing treatment due to adverse events (most commonly nausea, diarrhea, vomiting or fatigue; 7% vs 8%), although a lower proportion of patients in the APV600/RTV arm experienced drug-related oral/perioral paresthesia (2% vs 8%). Eleven (73%) of 15 patients who had HIV-1 RNA <200 copies/mL at week 24 and chose to continue study treatment maintained this level of virologic suppression at follow-up 24 weeks later. CONCLUSIONS: APV600 RTV BID was similar to or better than APV1200 BID in virologic response. Virologic results in a small number of patients who continued treatment for 24 weeks post-study suggest that virologic suppression with APV600 RTV BID is durable