Hypothesis Testing of a Single Mean and Single Proportion

A strategy for the generation of specific human antibodies by directed evolution and phage display An example of a single-chain antibody fragment that neutralizes a major component of scorpion venom Lidia Rian ˜ o-Umbarila, Victor Rivelino Jua ´ rez-Gonza ´ lez, Timoteo Olamendi-Portugal, Mauricio Ortı ´z-Leo ´ n, Lourival Domingos Possani and Baltazar Becerril Department of Molecular Medicine and Bioprocesses, Institute of Biotechnology, National Autonomous University of Mexico, Cuernavaca, Mexico In recent years, the demand for antibodies for thera- peutic purposes has increased [1]. To cope with this demand, some technologies have been adapted to gen- erate and improve these antibodies [2,3]. Two of these methods are phage display [4,5] and directed evolution [6,7]. These technologies have allowed the generation and improvement of different antibodies, which now reach affinities similar to those of a secondary immuno- logical response [3]. Depending on the purpose for which the antibody fragments are intended, several expression formats have been developed [8]. The tendency to use smaller molecule formats [single-chain antibody fragment (scFv); 25 kDa], is due to their increased biodistribution, diminished immunogenic characteristics and clearance properties [9]. Display of antibody fragment libraries on the surface of filamen- tous phages has replaced hybridoma technology for the selection of human antibodies through the creation of large repertoires in vitro [10]. This process begins with the cloning and expression of cDNAs encoding the variable regions of the H and L chains of antibod- ies (V H and V L ), allowing the in vitro generation of Keywords affinity maturation; directed evolution; human scFv library; phage display; scorpion toxin Correspondence B. Becerril, Av. Universidad No. 2001, Colonia Chamilpa, Cuernavaca 62210 Mexico Tel: +52 7773 291669 E-mail: baltazar@ibt.unam.mx Note The sequences reported have been depos- ited in the GenBank database under acces- sion nos. AY781338, AY781339, AY781340, AY781341 and AY781342; corresponding to scFvs: 3F, 6F, 610 A, 6009F and C1. (Received 9 March 2005, revised 21 March 2005, accepted 28 March 2005) doi:10.1111/j.1742-4658.2005.04687.x This study describes the construction of a library of single-chain antibody fragments (scFvs) from a single human donor by individual amplification of all heavy and light variable domains (1.1 · 10 8 recombinants). The lib- rary was panned using the phage display technique, which allowed selection of specific scFvs (3F and C1) capable of recognizing Cn2, the major toxic component of Centruroides noxius scorpion venom. The scFv 3F was matured in vitro by three cycles of directed evolution. The use of stringent conditions in the third cycle allowed the selection of several improved clones. The best scFv obtained (6009F) was improved in terms of its affin- ity by 446-fold, from 183 nm (3F) to 410 pm. This scFv 6009F was able to neutralize 2 LD 50 of Cn2 toxin when a 1 : 10 molar ratio of toxin-to-anti- body fragment was used. It was also able to neutralize 2 LD 50 of the whole venom. These results pave the way for the future generation of recombin- ant human antivenoms. Abbreviat Hypothesis Testing of a Single Mean and Single Proportion Hypothesis Testing of a Single Mean and Single Proportion By: OpenStaxCollege Hypothesis Testing of a Single Mean and Single Proportion Class Time: Names: Student Learning Outcomes • The student will select the appropriate distributions to use in each case • The student will conduct hypothesis tests and interpret the results Television SurveyIn a recent survey, it was stated that Americans watch television on average four hours per day Assume that σ = Using your class as the sample, conduct a hypothesis test to determine if the average for students at your school is lower H0: _ Ha: _ In words, define the random variable = The distribution to use for the test is _ Determine the test statistic using your data Draw a graph and label it appropriately.Shade the actual level of significance Graph: 1/3 Hypothesis Testing of a Single Mean and Single Proportion Determine the p-value Do you or you not reject the null hypothesis? Why? Write a clear conclusion using a complete sentence Language SurveyAbout 42.3% of Californians and 19.6% of all Americans over age five speak a language other than English at home Using your class as the sample, conduct a hypothesis test to determine if the percent of the students at your school who speak a language other than English at home is different from 42.3% H0: _ Ha: _ In words, define the random variable = _ The distribution to use for the test is Determine the test statistic using your data Draw a graph and label it appropriately Shade the actual level of significance Graph: Determine the p-value Do you or you not reject the null hypothesis? Why? Write a clear conclusion using a complete sentence Jeans SurveySuppose that young adults own an average of three pairs of jeans Survey eight people from your class to determine if the average is higher than three Assume the population is normal 2/3 Hypothesis Testing of a Single Mean and Single Proportion H0: _ Ha: _ In words, define the random variable = The distribution to use for the test is _ Determine the test statistic using your data Draw a graph and label it appropriately Shade the actual level of significance Graph: Determine the p-value Do you or you not reject the null hypothesis? Why? Write a clear conclusion using a complete sentence 3/3 [...]... or research hypothesis The usual notation is: pronounced H ‘nought’ H0: — the ‘null’ hypothesis HA: — the ‘alternative’ or ‘research’ hypothesis The null hypothesis (H0) will always state that the parameter equals the value specified in the 13 alternative hypothesis (HA) Concepts of Hypothesis Testing… Consider Example 12.1 (mean computer assembly time) again Rather than estimate the mean assembly... manager knows that the accounts are approximately normally distributed with a standard deviation of $65 Can the manager conclude from this that the new system will be cost-effective? 22 Example 1… IDENTIFY The system will be cost effective if the mean account balance for all customers is greater than $170 We express this belief as our research hypothesis, that is: HA: µ > 170 (this is what we want... 28 Example 1… COMPUTE All that’s left to do is calculate compare it to 170 and we can calculate this based on any level of significance (α) we want… 29 Example 1… COMPUTE At a 5% significance level (i.e α =0.05), we get Solving we compute = 175.34 Since our sample mean (178) is greater than the critical value we calculated (175.34), we reject the null hypothesis in favour of H1, i.e that: µ > 170 and... decisions that can be made: Conclude that there is enough evidence to support the alternative hypothesis (also stated as: rejecting the null hypothesis in favour of the alternative) Conclude that there is not enough evidence to support the alternative hypothesis (also stated as: not rejecting the null hypothesis in favour of the alternative) NOTE: we do not say that we accept the null hypothesis 17... manually), and The p-value approach (which is generally used with a computer and statistical software) We will explore both in turn… 25 The Rejection Region Method The rejection region is a range of values such that, if the test statistic falls into that range, the null hypothesis is rejected in favour of the alternative hypothesis Define the value of x that is just large enough to reject the null hypothesis. .. Concepts of Hypothesis Testing… Once the null and alternative hypotheses are stated, the next step is to randomly sample the population and calculate a test statistic (in this example, the sample mean) If the test statistic’s value is inconsistent with the null hypothesis we reject the null hypothesis and infer that the alternative hypothesis is true 18 Concepts of Hypothesis Testing… For example, if... H0 in favour of HA… 32 Example 1: The Big Picture Again 05 H0: µ = 170 0 Z HA: µ > 170 Z.05=1.645 z = 2.46 Reject H0 in favour of 33 Example 1: In summary… • Step 1: Null and alternative hypotheses: H0: µ = 170 HA: µ > 170 • Step 2: Test statistic: x−µ Z= σ n Z has a standard normal distribution as X Hindawi Publishing Corporation EURASIP Journal on Wireless Communications and Networking Volume 2010, Article ID 719523, 16 pages doi:10.1155/2010/719523 Research Article Design and Implementation of a Single-Frequency Mesh Network Using OpenAirInterface Florian Kaltenberger, Rizwan Ghaffar, Raymond Knopp, Hicham Anouar, and Christian Bonnet Eurecom, 2229, Route des Cretes, B.P. 193, 06904 Sophia Antipolis, France Correspondence should be addressed to Florian Kaltenberger, florian.kaltenberger@eurecom.fr Received 1 June 2009; Revised 20 October 2009; Accepted 11 January 2010 Academic Editor: Faouzi Bader Copyright © 2010 Florian Kaltenberger et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. OpenAirInterface is an experimental open-source real-time hardware and software platform for experimentation in wireless communications and signal processing. With the help of OpenAirInterface, researchers can demonstrate novel ideas quickly and verify them in a realistic environment. Its current implementation provides a full open-source software modem comprising physical and link layer functionalities for cellular and mesh network topologies. The physical (PHY) layer of the platform targets fourth generation wireless networks and thus uses orthogonal frequency division multiple access (OFDMA) together with multiple-input multiple-output (MIMO) techniques. The current hardware supports 5 MHz bandwidth and two transmit/receive antennas. The media access (MAC) layer of the platform supports an abundant two-way signaling for enabling collaboration, scheduling protocols, as well as traffic and channel measurements. In this paper, we focus on the mesh topology and show how to implement a single-frequency mesh network with OpenAirInterface. The key ingredients to enable such a network are a dual- stream MIMO receiver structure and a distributed network synchronization algorithm. We show how to implement these two algorithms in real-time on the OpenAirInterface platform. Further more, we provide results from field trials and compare them to the simulation results. 1. Introduction The design and implementation of next generation wireless networks is a very challenging task. To ensure optimal performance it is necessary to carry out performance eval- uations and field trials in parallel to standard development. Easily reconfigurable testbeds are a convenient way to investigate new ideas and to tackle many problems at an early development stage. Novel ideas for wireless networks are usually first studied using computer simulations based on some kind of model of the network, the hardware and the radio channel. These models usually make assumptions in order to simplify or isolate the problem at hand. However, it might turn out that the assumptions are not fulfilled in a real environment. An easily reconfigurable experimental platform allows to study novel algorithms under realistic conditions. Comparing simulation results with results from lab tests and field trials reveals if initial assumptions were correct or if they need to be refined. This paper presents the Eurecom testbed OpenAirIn- terface, which is an experimental real-time, open-source hardware and software platform for future wireless networks. OpenAirInterface can be seen as a mock standard for realistic experimentation purposes which retains the salient features of a real radio system, without all -2851$/ 2) 9H W H U L Q D U \  6FLHQFH J. Vet. Sci. (2004), / 5 (3), 263–265 Persistent occurrence of a single Streptococcus equi subsp. zooepidemicus clone in the pig and monkey population in Indonesia Siti Isrina Oktavia Salasia 1,4 , I Wayan Teguh Wibawan 2 , Fachriyan H. Pasaribu 2 , Amir Abdulmawjood 3 , Christoph Lämmler 4, * 1 Faculty of Veterinary Medicine, Gadjah Mada University, Sekip Unit II, Yogyakarta 55281, Indonesia 2 Faculty of Veterinary Medicine, Institut Pertanian Bogor, Jl. Taman Kencana no. 3, Bogor 16151, Indonesia 3 Institut für Tierärztliche Nahrungsmittelkunde, Justus-Liebig-Universität Gießen, Frankfurter Str. 92, D-35392 Gießen, Germany 4 Institut für Pharmakologie und Toxikologie, Justus-Liebig-Universität Gießen, Frankfurter Str. 107, D-35392 Gießen, Germany In the present study 41 mucoid growing Streptococcus equi subsp. zooepidemicus strains (37 strains isolated from healthy two from diseased pigs, two strains isolated from healthy monkeys) appeared to be phenotypically and genotypically identical to mucoid growing S. equi subsp. zooepidemicus strains isolated from a previously described outbreak among the pig and monkey population on the island of Bali, Indonesia. These findings indicate that the mucoid growing S. equi subsp. zooepidemicus clone was still present in the pig and monkey population in Indonesia. Key words: S. equi subsp. zooepidemicus , pig, monkey, epi- demiological relation Streptococcus equi subsp. zooepidemicus is well known from infections of a wide variety of animals, including pigs, sheep, cows, goats, foxes, birds, rabbits, guinea pigs, and monkeys [11,15,16]. All these animals might be potential reservoirs for infections of humans. Cases of human infections with S. equi subsp. zooepidemicus have been reported, and such infections are frequently associated with the consumption of homemade cheese or unpasteurized milk [3,4,6]. The isolation of S. equi subsp. zooepidemicus from humans has been described in cases of endocarditis [13], pneumonia [14], meningitis [8,12], septic arthritis [2,9], and cervical lymphadenitis [10]. At the beginning of 1994, a disease outbreak among pigs and monkeys was reported on the island of Bali, Indonesia. The first cases were reported among animals of a pig owner in a small village on the island of Bali. In the following weeks and months, the outbreak spread rapidly to the surrounding districts in Bali, to other islands of Indonesia and into a monkey population. The diseased animals showed clinical symptoms such as painful swelling of the joint, respiratory disturbances, and diarrhea. Most of the animals died within a few days. The postmortem examination of the pigs and monkeys revealed signs of polyarthritis, bronchopneumonia, pleuritis, epicarditis, endocarditis, and meningitis [5]. The bacteriological examination resulted in the isolation of streptococci of Lancefield group C. The bacteria were identified as S. equi subsp. zooepidemicus . A DNA fingerprinting revealed identical profiles, indicating that a single virulent clone was the causative agent of the various pig and monkey infections on the island of Bali and the other islands of Indonesia [15]. These findings raises the question whether the bacterial clone discovered in 1994 remained to be present in the pig or monkey population. The present study was designed to further characterize S. equi subsp. zooepidemicus isolated from healthy and diseased pigs and monkeys on the islands of Bali and Java, Indonesia between the years 1995 to 1998. A total of 49 β -hemolytic streptococci were investigated in this study. Thirty nine streptococci were isolated from tonsils of 39 healthy pigs in the slaughter house in Denpasar, Bali, Indonesia, during a period of 4 years (1995, one strain; 1996, three strains; 1997, two strains; 1998, 33 strains), two streptococci were isolated in 1997 from two diseased pigs in Yogyakarta, Central Java, Indonesia, and two Open Access Available online http://arthritis-research.com/content/9/2/R38 Page 1 of 11 (page number not for citation purposes) Vol 9 No 2 Research article Vaccination response to tetanus toxoid and 23-valent pneumococcal vaccines following administration of a single dose of abatacept: a randomized, open-label, parallel group study in healthy subjects Lee Tay 1 , Francisco Leon 2 , George Vratsanos 3 , Ralph Raymond 4 and Michael Corbo 3 1 Clinical Discovery, Bristol-Myers Squibb, PO Box 4000, Princeton, NJ 08543-4000, USA 2 Clinical Development, Inflammatory Diseases, MedImmune, 1 MedImmune Way, Gaithersburg, MD 20878, USA 3 Global Clinical Research, Immunology, PO Box 4000, Bristol-Myers Squibb, Princeton, NJ 08543-4000, USA 4 Global Biometric Sciences, PO Box 4000, Bristol-Myers Squibb, Princeton, NJ 08543-4000, USA Corresponding author: Lee Tay, lee.tay@bms.com Received: 31 Jul 2006 Revisions requested: 31 Aug 2006 Revisions received: 26 Mar 2007 Accepted: 10 Apr 2007 Published: 10 Apr 2007 Arthritis Research & Therapy 2007, 9:R38 (doi:10.1186/ar2174) This article is online at: http://arthritis-research.com/content/9/2/R38 © 2007 Tay et al., licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract The effect of abatacept, a selective T-cell co-stimulation modulator, on vaccination has not been previously investigated. In this open-label, single-dose, randomized, parallel-group, controlled study, the effect of a single 750 mg infusion of abatacept on the antibody response to the intramuscular tetanus toxoid vaccine (primarily a memory response to a T-cell- dependent peptide antigen) and the intramuscular 23-valent pneumococcal vaccine (a less T-cell-dependent response to a polysaccharide antigen) was measured in 80 normal healthy volunteers. Subjects were uniformly randomized to receive one of four treatments: Group A (control group), subjects received vaccines on day 1 only; Group B, subjects received vaccines 2 weeks before abatacept; Group C, subjects received vaccines 2 weeks after abatacept; and Group D, subjects received vaccines 8 weeks after abatacept. Anti-tetanus and anti- pneumococcal (Danish serotypes 2, 6B, 8, 9V, 14, 19F and 23F) antibody titers were measured 14 and 28 days after vaccination. While there were no statistically significant differences between the dosing groups, geometric mean titers following tetanus or pneumococcal vaccination were generally lower in subjects who were vaccinated 2 weeks after receiving abatacept, compared with control subjects. A positive response (defined as a twofold increase in antibody titer from baseline) to tetanus vaccination at 28 days was seen, however, in ≥ 60% of subjects across all treatment groups versus 75% of control subjects. Similarly, over 70% of abatacept-treated subjects versus all control subjects (100%) responded to at least three pneumococcal serotypes, and approximately 25–30% of abatacept-treated subjects versus 45% of control subjects responded to at least six serotypes. Introduction Treatment with abatacept has demonstrated efficacy in patients with active rheumatoid arthritis (RA) and an inade- quate response to methotrexate, and in those with an inade- quate response to anti-TNF therapy [1-3]. Abatacept is a soluble fusion protein consisting of the extracellular domain of human cytotoxic T-lymphocyte-associated antigen-4 linked to the Fc (hinge, CH2 and CH3 domains) portion of human IgG 1 , which has been modified to be noncomplement fixing. Abata- cept is the first in a class of agents for the treatment of RA that selectively modulates the CD80/CD86:CD28 co-stimulatory signal required for full T-cell activation [4]. Activation of T cells usually requires two signals from ... sentence Language SurveyAbout 42.3% of Californians and 19.6% of all Americans over age five speak a language other than English at home Using your class as the sample, conduct a hypothesis test to... statistic using your data Draw a graph and label it appropriately Shade the actual level of significance Graph: Determine the p-value Do you or you not reject the null hypothesis? Why? Write a. .. average is higher than three Assume the population is normal 2/3 Hypothesis Testing of a Single Mean and Single Proportion H0: _ Ha: _ In words, define the random variable =