ADA deficiency

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Polyethylene Glycol-Conjugated Adenosine Deaminase (ADA) Therapy Provides Temporary Immune Reconstitution to a Child with Delayed-Onset ADA Deficiency

Polyethylene Glycol-Conjugated Adenosine Deaminase (ADA) Therapy Provides Temporary Immune Reconstitution to a Child with Delayed-Onset ADA Deficiency

We describe the effects of polyethylene glycol-conjugated adenosine deaminase (ADA) replacement therapy on lymphocyte counts, activation, apoptosis, proliferation, and cytokine secretion in a 14-month-old girl with “delayed-onset” ADA deficiency and marked immunodysregulation. Pretreatment lymphopenia affected T cells (CD4, 150/ ␮ l; CD8, 459/ ␮ l), B cells (16/ ␮ l), and NK cells (55/ ␮ l). T cells were uniformly activated and largely apoptotic (CD4, 59%; CD8, 82%); and T-cell-dependent cytokine levels in plasma were elevated, including the levels of interleukin 2 (IL-2; 26 pg/ml), IL-4 (81 pg/ml), IL-5 (46 pg/ml), gamma interferon (1,430 pg/ml), tumor necrosis factor alpha (210 pg/ml), and IL-10 (168 pg/ml). Mitogen-stimulated peripheral blood mononuclear cells show reduced IL-2 secretion and proliferation. During the first 5 months of therapy there was clinical improvement and partial immune reconstitution, with nearly normal lymphocyte subset numbers, reduced T-cell activation and CD4-cell apoptosis, and decreased plasma cytokine levels. In parallel, IL-2 secretion and the lymphocyte mitogenic response improved. Between 4 and 7 months, immunoglobulin G antibodies to bovine ADA developed and resulted in the complete reversal of immune recovery.

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Identification of a point mutation resulting in a heat labile adenosine deaminase (ADA) in two unrelated children with partial ADA deficiency

Identification of a point mutation resulting in a heat labile adenosine deaminase (ADA) in two unrelated children with partial ADA deficiency

We have determined the mutation in a child with partial adenosine deaminase (ADA) deficiency who is phenotypically homozygous for a mutant ADA gene encoding a heat- labile enzyme (Am. J. Hum. Genet. 38: 13-25). Sequencing of cDNA demonstrated a C to A transversion that results in the replacement of a proline by a glutamine residue at codon 297. As this mutation generated a new recognition site in exon 10 of genomic DNA for the enzyme Alu I, Southern blot analysis was used to establish that this child was indeed homozygous for the mutation. The abnormal restriction fragment generated by this mutation was also found in a second partially ADA-deficient patient who phenotypically is a genetic compound and also expresses a heat-labile ADA (in addition to a more acidic than normal ADA) (Am. J. Hum. Genet. 38: 13-25). Sequencing of cDNA clones from the second patient established the identical codon 297 mutation. Transfection of the mutant cDNA into

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IgG antibody response to polyethylene glycol modified adenosine deaminase in patients with adenosine deaminase deficiency

IgG antibody response to polyethylene glycol modified adenosine deaminase in patients with adenosine deaminase deficiency

Polyethylene glycol (PEG)-modified bovine adenosine deaminase (ADA) is used for replacement therapy of severe combined immunodeficiency disease due to inherited ADA deficiency. We monitored IgG anti-ADA antibody in 17 patients treated by intramuscular injections of PEG-ADA for 1 to greater than 5.5 yr. ELISA-detectable anti-ADA IgG appeared in 10 patients, usually between the third and eighth months of treatment. Anti- ADA levels did not correlate with trough plasma ADA activity, which averaged 1.8-5 times normal blood (erythrocyte) ADA activity, depending on dose (15-60 U/kg per wk). ELISA- detectable anti-ADA antibodies were directed primarily at bovine-specific peptide (rather than PEG-containing) epitopes. Enhanced enzyme clearance, mediated by antibody that directly inhibited native and PEG-modified bovine ADA, and native, but not PEG-modified human ADA, occurred in two patients. In one, tolerance was induced; in the second, twice weekly injections of PEG-ADA compensated for accelerated clearance. We speculate that inhibitory antibodies recognize conserved, relatively PEG-free epitope(s) encompassing the active site, and that in human, but not bovine, ADA a PEG-attachment site "shields" the active site from immune recognition. We conclude that PEG-modification largely prevents the development of high affinity, or high levels of clearing antibodies to bovine ADA, and that PEG-modified human ADA should be further investigated as a possible treatment for ADA deficiency.

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Adenosine deaminase deficiency increases thymic apoptosis and causes defective T cell receptor signaling

Adenosine deaminase deficiency increases thymic apoptosis and causes defective T cell receptor signaling

A two-stage genetic engineering strategy was used to produce ADA-deficient mice that retain many of the features associated with ADA deficiency in humans (13, 14). These mice develop a combined immunodeficien- cy that is associated with profound disturbances in purine metabolism (13). The ability to analyze tissues from ADA-deficient mice, an experimental approach not possible with ADA-deficient humans, enabled us to make novel immunological and metabolic observations. Analysis of tissue-associated metabolic disturbances in these mice revealed that absolute increases in ADA sub- strates are greatest in the thymus and spleen (15), sug- gesting that metabolic disturbances in these major immune organs play a major role in the ensuing immunodeficiency (13). Here we report a detailed analy- sis of the impact of ADA deficiency on intrathymic T cell development and on T cell receptor–mediated (TCR-mediated) signaling in the periphery. Our results show that ADA deficiency is associated with enhanced thymocyte apoptosis and impaired TCR signaling.

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Purine nucleoside metabolism in the erythrocytes of patients with adenosine deaminase deficiency and severe combined immunodeficiency

Purine nucleoside metabolism in the erythrocytes of patients with adenosine deaminase deficiency and severe combined immunodeficiency

nucleosides was studied in erythrocytes from normal individuals, four ADA-deficiency patients, and two heterozygous individuals. ADA deficiency in intake erythrocytes was confirmed by a very sensitive ammonia-liberation technique. Erythrocytic ADA activity in three heterozygous individuals (0.07,0.08, and 0.14 mumolar units/ml of packed cells) was between that of the four normal controls (0.20-0.37 mumol/ml) and the ADA-deficient patients (no activity). In vitro, adenosine was incorporated principally into IMP in the heterozygous and normal individuals but into the adenosine nucleotides in the ADa- deficient patients. Coformycin (3-beta-D-ribofuranosyl-6,7,8-trihydroimidazo[4,5-4] [1,3] diazepin-8 (R)-ol), a potent inhibitor of ADA, made possible incorporation of adenosine nucleotides in the ADA-deficient patients...

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Pegademase bovine (PEG-ADA) for the treatment of infants and children with severe combined immunodeficiency (SCID

Pegademase bovine (PEG-ADA) for the treatment of infants and children with severe combined immunodeficiency (SCID

Adenosine deaminase (ADA) deficiency is a rare inherited disorder of purine metabolism characterized by severe and recurrent infection, failure to thrive and meta- bolic abnormalities. Absence of the enzyme ADA allows accumulation of toxic metabolites resulting in a complete or partial deficiency of both cell-mediated and humoral immunity. ADA severe combined immune deficiency (SCID) is fatal within the first months of life if left untreated. Hematopoietic stem cell transplant is cura- tive but dependent on a good donor match. Other therapeutic options include enzyme replacement therapy (ERT) with pegademase bovine (hereon referred to as PEG-ADA) and more recently, gene therapy. PEG-ADA was first used to treat ADA deficiency in 1986 and to date more than 150 patients worldwide have received this treatment. It is well tolerated and can restore immune function to protective levels but long-term follow up suggests that immune recovery is incomplete. The precise role of PEG- ADA alongside other treatment options is still to be determined but to date it has allowed stabilization of patients awaiting more definitive treatment and clinical well-being in individuals treated for more prolonged periods.

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ADA ESTIMATION IN BODY FLUIDS OF TUBERCULOSIS PATIENTS

ADA ESTIMATION IN BODY FLUIDS OF TUBERCULOSIS PATIENTS

technically more demanding, most of the times diagnosis is based on radiological features, clinical features and positive tuberculin testing. Recently, attempts are on to find most simple techniques which are reliable more feasible; less costly and giving quick results and are largely comparable with standard techniques. In the present study, ADA (Adenosine deaminase) estimation in blood and body fluids of tubercular patients are studied.

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Ada Lovelace’s Legacy for Computation History

Ada Lovelace’s Legacy for Computation History

The drama of her parents' separation, coupled with family controversies [14] revealed to English society, did not hinder their intellectual development. [10] The marriage between Lord Byron and Annabelle was brief and ended five (5) months after Ada's birth [9, 10, 14]. Her mother learned that Augusta was the name of one of her ex-husband's lovers, so she decided to call Augusta only Ada [10, 14, 15]. During her childhood she was educated not only in the art of music, reading and writing, but mainly in the mathematics of arithmetic logic, following a disciplinary routine through tutors such as Mary Somerville Mathematics [4, 10, 11, 14, 15, 16, 17], first woman to join the Royal Society of Astronomy. In some letters Ada wrote to her mother, especially in the correspondence of June 1, 1826 [10], while Annabelle traveled, one can see how much an applied child she was:

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Implementing atomic actions in Ada 95

Implementing atomic actions in Ada 95

Arguably, high-level support is not needed and the re- quired functionality can be programmed with lower-level primitives. For example, some attempts have been made to program conversations in Ada 83 [9], [10], [11]; however, these were severely hampered by the lack of suitable lan- guage support. For instance, Romanovsky and Strigini [11] only allow parallelism to exist inside a conversation; the ap- proach is not appropriate if a collection of pre-existing tasks wish to participate collectively in a conversation. None of these attempts address how to structure atomic actions with both forward and backward error recovery in Ada 95.

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Paradoxical expression of adenosine deaminase in T cells cultured from a patient with adenosine deaminase deficiency and combine immunodeficiency

Paradoxical expression of adenosine deaminase in T cells cultured from a patient with adenosine deaminase deficiency and combine immunodeficiency

T lymphocytes cultured from a patient (T.D.) with adenosine deaminase (ADA) deficiency expressed ADA activity in the normal range, inconsistent with her severe immunodeficiency, metabolic abnormalities, and with the absence of ADA activity in her B lymphocytes and other nucleated hematopoietic cells. ADA from T.D. T cells had normal Km, heat stability, and sensitivity to ADA inhibitors. Examination of HLA phenotype and polymorphic DNA loci indicated that T.D. was neither chimeric nor a genetic mosaic. Amplified and subcloned ADA cDNA from ADA+ T.D. T cells was shown by allele-specific oligonucleotide

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Peritoneal Tuberculosis: Looking beyond the Typical Pathology

Peritoneal Tuberculosis: Looking beyond the Typical Pathology

TbP is still a medical concern in developing countries but is relatively uncommon in developed countries. However, due to increases of international travel and the frequency of immune suppressive diseases such as ac- quired immune deficiency syndrome (AIDS), physicians worldwide should be aware of TbP. Unless a high de- gree of suspicion is maintained, the diagnosis can easily be missed or delayed, resulting in increased morbidity and mortality [6].

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Dynamic Routing for ADA in Wireless Sensor Networks

Dynamic Routing for ADA in Wireless Sensor Networks

Abstract: Sensor webs consisting of nodes with limited battery power and wireless communications are deployed to collect useful information from the field[1]. Gathering sensed information in an energy efficient manner is critical to operating the sensor network for a long period of time. Data collection problem is defined where, in a round of communication, each sensor node has a packet to be sent to the distant base station. There is some fixed amount of energy cost in the electronics when transmitting or receiving a packet and a variable cost when transmitting a packet which depends on the distance of transmission. If each node transmits its sensed data directly to the base station, then it will deplete its power quickly. Data aggregation[3][5] has been widely recognized as an efficient method to reduce energy consumption[4] in wireless sensor networks, which can support a wide range of applications such as monitoring temperature[4], humidity, level, speed etc. The data sampled by the same kind of sensors have much redundancy since the sensor nodes are usually quite dense in wireless sensor networks. To make data aggregation more efficient, the packets with the same attribute, defined as the identifier of different data sampled by different sensors such as temperature sensors, humidity sensors, etc., should be gathered together. However, to the best of our knowledge, present data aggregation mechanisms did not take packet attribute into consideration. Following this paradigm, numerous data aggregation schemes [6], [7], [8],[9],[10], [11], [12], [13], [14], [15], [16], [7], [18] have been proposed to save the limited energy on sensor nodes in WSNs. In this paper, we take the lead in introducing packet attribute into data aggregation and propose an Attribute- aware Data Aggregation(ADA) mechanism using Dynamic Routing which can make packets with the same attribute convergent as much as possible and therefore improve the efficiency of data aggregation.

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Ada Boost Ensemble Classifier for Identification of Somatic Mutations

Ada Boost Ensemble Classifier for Identification of Somatic Mutations

AdaBoost (Adaptive Boost) algorithm is one type of boosting technique. It was introduced by Freund and Schapiro. In the AdaBoost technique the weighted forms of equal training data will be utilized in spite of random sample data usage. The single trained data is used number of times and the groups of classifiers with improved enactment will be produced by using AdaBoost algorithm. To generate the last outstanding classifier [11], Adaboost algorithm prepares a group of classifiers by using the weak classifier (wrongly classified learner)[12].For the training data weights will be given and classification is to be performed, based on the weighted version of that data set of weak classifiers generated consecutively then the weights will be reweighted based on the quality of the performed classifiers. For every iteration, training data never changes and classification performs according to the misclassification of the preceding classifiers. The weak learners concentrate on the patterns which were not classified effectively. It continues this process until we get a strong base learner to reach maximum accuracy. AdaBoost [13] focuses on reduction of errors during learning. The weights of the wrongly classified tuples will remain constant and is not varied. AdaBoost has the advantage of not considering a single characteristic, but considers a set of labels with high probabilities. It puts its focus on the labels that were wrongly classified [14] In order to attain the accurate and desired output and the minimized pseudo loss is needed. Boosting methods (Ada Boost) can effectively be used with large datasets. Use of these complex algorithms will reduce the errors of the classifier. The AdaBoost algorithm implemented on somatic mutational data sets is shown below.

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THE INTERRELATIONSHIP BETWEEN UMRAO JAAN ADA, THE TEXT, AND UMRAO JAAN, THE FILM

THE INTERRELATIONSHIP BETWEEN UMRAO JAAN ADA, THE TEXT, AND UMRAO JAAN, THE FILM

According to Kettenbelt there are three concepts of mediality: multi-, trans- and intermediality. “Multimediality refers to the occurrence where there are many media in one and the same object.” In the movie, Umrao Jaan, there is the use of more than one media, i.e. musical, pictorial and choreographed movements. “Transmediality refers to the transfer from one medium to another medium (media change)” (Kettenbelt 2008). Here, the novel, Umrao Jaan Ada, presented through the medium of written words has been transferred to the media of audio-visual representation in the movie Umrao Jaan. “Intermediality refers to the co- relation of media in the sense of mutual influences between media” (Kettenbelt 2008). Contemporary idea of intermediality could be related with the idea of “Buhnen Kompositionen(stage compositions) of Wassily Kandinsky”. According to Kandinsky, “the

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Travel Times (or Journeys with Ada)

Travel Times (or Journeys with Ada)

As the journey wears on time is stretching for Ada. There is a withering of activity in the carriage, as less and less seems to happen. People adopt an automaton position, hands clasped in their laps, eyes resting ahead. Their typical activities, of reading, gazing and working (as determined by the rail survey), remain unchanged, fixed. As the train rolls on, without stopping, time becomes ever more sluggish, thickening around tired limbs like treacle. Travel time has an inertia. Time tends to stretch, activities tend to diminish. It takes effort to overcome this inertia. The view tends simply goes on, the coffee tends cool, bones tend to stiffen. To pack up and leave the train involves speeding up, overcoming this inertia, packing up the travelling self, putting away the book and water bottle, ready to adapt and unpack into a new space – a street, car, office or home.

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Prevalence of iodine deficiency and associated factors among pregnant women in Ada district, Oromia region, Ethiopia: a cross  sectional study

Prevalence of iodine deficiency and associated factors among pregnant women in Ada district, Oromia region, Ethiopia: a cross sectional study

Studies over the past decade have indicated the public health significance of IDD in Ethiopia. A national micro- nutrient survey in 2005 reported 35.8% total goiter rates (TGR) in women of reproductive age [10]. In 2011 the International Council for the Control of Iodine Deficiency Disorders (ICCIDD) estimated that 12 million school age children (SAC) were living with inadequate iodine (4) and around 66 million of the Ethiopian population were at risk of iodine deficiency [11]. A few studies before Ethiopian mandatory salt iodization program also reported a high level of iodine deficiency in pregnant women. A study conducted in Sidama zone reported a median urinary iodine concentration (UIC) of 15 μ g/L and TGR of 49% [12]. Furthermore, a study conducted in 2012, a few months after mandatory salt iodization, reported a median UIC of 58 μ g/L and UIC less than 150 μ g/L in 82.8% of pregnant women [13]. Recognizing the public health significance of iodine deficiency in Ethiopia, the Council of Ministers passed new salt legislation in February 2011 and the government started implementing a mandatory salt iodization program and public promotion in 2012 [11]. However, studies addressing iodine status of preg- nant women after the introduction of the mandatory salt iodization program are lacking in Ethiopia.

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Adenosine deaminase (ADA) deficiency due to deletion of the ADA gene promoter and first exon by homologous recombination between two Alu elements

Adenosine deaminase (ADA) deficiency due to deletion of the ADA gene promoter and first exon by homologous recombination between two Alu elements

In 15-20% of children with severe combined immunodeficiency (SCID), the underlying defect is adenosine deaminase (ADA) deficiency. The goal of this study was to determine the precise molecular defect in a patient with ADA-deficient SCID whom we previously have shown to have a total absence of ADA mRNA and a structural alteration of the ADA gene. By detailed Southern analysis, we now have determined that the structural alteration is a deletion of approximately 3.3 kb, which included exon 1 and the promoter region of the ADA gene. DNA sequence analysis demonstrates that the deletion created a novel, complete Alu repeat by homologous recombination between two existing Alu repeats that flanked the deletion. The 26-bp recombination joint in the Alu sequence includes the 10-bp "B" sequence homologous to the RNA polymerase III promoter. This is the first example of homologous recombination involving the B sequence in Alu repeats. Similar recombination events have been identified involving Alu repeats in which the recombination joint was located between the A and B sequences of the polymerase III split promoter. The

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The Deadline Floor Protocol and Ada

The Deadline Floor Protocol and Ada

• Protected objects shared between EDF-scheduled and priority-scheduled tasks. In order to fit into the Ada framework for scheduling mixed systems, it is necessary to allow some protected objects to have both a priority ceiling and a deadline floor. The rules are simple, if the ceiling of the protected object is a FIFO-within priority level, the task’s active deadline is not updated while executing within the protected object (i.e. there is no need to have a deadline floor). If the ceiling priority is an EDF-within priority level, the task’s active deadline is updated (i.e. it does need a floor). Nested protected object across levels require further consideration.

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Provide Diagnostics and Polling to your ADA Compliant Emergency Phone Customers

Provide Diagnostics and Polling to your ADA Compliant Emergency Phone Customers

The 1600A Series ADA Compliant Emergency Phones are designed to provide quick and reliable handsfree communica- tion over the public switched telephone network. All 1600A Series phones meet ADA requirements for elevator/emergency telephones, and can be pro- grammed from any Touch Tone phone. The phones can dial up to 5 programmable emergency num- bers, as well as 2 central station numbers. In addition, the E-1600-20A features an "Info" but- ton that will dial up to 3 non-emergency num- bers.

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