Miracle-dz/UniFAR-FTUs huggingface dataset:
Analyzing the Handoff of DNA from UvrA to UvrB Utilizing DNA-Protein Photoaffinity Labeling*♦

To better define the molecular architecture of nucleotide excision repair intermediates it is necessary to identify the specific domains of UvrA, UvrB, and UvrC that are in close proximity to DNA damage during the repair process. One key step of nucleotide excision repair that is poorly understood is the transfer of damaged DNA from UvrA to UvrB, prior to incision by UvrC. To study this transfer, we have utilized two types of arylazido-modified photoaffinity reagents that probe residues in the Uvr proteins that are closest to either the damaged or non-damaged strands. The damaged strand probes consisted of dNTP analogs linked to a terminal arylazido moiety. These analogs were incorporated into double-stranded DNA using DNA polymerase β and functioned as both the damage site and the cross-linking reagent. The non-damaged strand probe contained an arylazido moiety coupled to a phosphorothioate-modified backbone of an oligonucleotide opposite the damaged strand, which contained an internal fluorescein adduct. Six site-directed mutants of Bacillus caldotenax UvrB located in different domains within the protein (Y96A, E99A, R123A, R183E, F249A, and D510A), and two domain deletions (Δ2 and Δβ-hairpin), were assayed. Data gleaned from these mutants suggest that the handoff of damaged DNA from UvrA to UvrB proceeds in a three-step process: 1) UvrA and UvrB bind to the damaged site, with UvrA in direct contact; 2) a transfer reaction with UvrB contacting mostly the non-damaged DNA strand; 3) lesion engagement by the damage recognition pocket of UvrB with concomitant release of UvrA.
Selective antihypertensive action of moxonidine is mediated mainly by I1-imidazoline receptors in the rostral ventrolateral medulla.

The rostral ventrolateral medulla (RVLM) is the primary region maintaining vasomotor tone, and a site of action for central antihypertensive agents. In vitro [125I]p-iodoclonidine binding studies showed that moxonidine was selective for I1-imidazoline over alpha 2-adrenergic receptors in the RVLM. We identified efaroxan and SK&F 86466 as selective I1- and alpha 2-antagonists, respectively. We tested moxonidine's action within the RVLM of spontaneously hypertensive rats (SHRs) on I1-imidazoline or alpha 2-adrenergic receptors, and determined whether the RVLM mediates the action of systemic moxonidine. SHRs were anesthetized, paralyzed, and ventilated and the RVLM was localized by testing for a pressor response to 2 nmol glutamate. To test whether I1 or alpha 2 mediates hypotensive effects of moxonidine, the I1/alpha 2 antagonist efaroxan (4 nmol) or the alpha 2-blocker SK&F 86466 (10 nmol) was administered 15 min before 4 nmol moxonidine. Efaroxan elevated blood pressure and abolished the action of moxonidine, whereas alpha 2-blockade with SK&F 86466 slightly lowered blood pressure and only partially attenuated moxonidine's effect. The depressor effect of intravenous moxonidine (40 micrograms/kg) was reversed within 10 min by microinjection of 10 nmol efaroxan into the RVLM. Prior bilateral microinjections of efaroxan (10 nmol in 80 nl/site) into the RVLM prevented the hypotensive action of moxonidine given i.v. (40 micrograms/kg). Pharmacokinetic studies showed that at the peak vasodepressor response (8 min post-injection), [3H]moxonidine spread less than 1 mm from the injection site. Moxonidine is a centrally acting antihypertensive with a selective action on I1-imidazoline receptors in RVLM.
A Recombinant Measles Vaccine with Enhanced Resistance to Passive Immunity

Current measles vaccines suffer from poor effectiveness in young infants due primarily to the inhibitory effect of residual maternal immunity on vaccine responses. The development of a measles vaccine that resists such passive immunity would strongly contribute to the stalled effort toward measles eradication. In this concise communication, we show that a measles virus (MV) with enhanced hemagglutinin (H) expression and incorporation, termed MVvac2-H2, retained its enhanced immunogenicity, previously established in older mice, when administered to very young, genetically modified, MV-susceptible mice in the presence of passive anti-measles immunity. This immunity level mimics the sub-neutralizing immunity prevalent in infants too young to be vaccinated. Additionally, toward a more physiological small animal model of maternal anti-measles immunity interference, we document vertical transfer of passive anti-MV immunity in genetically-modified, MV susceptible mice and show in this physiological model a better MVvac2-H2 immunogenic profile than that of the parental vaccine strain. In sum, these data support the notion that enhancing MV hemagglutinin incorporation can circumvent in vivo neutralization. This strategy merits additional exploration as an alternative pediatric measles vaccine.
The role of regulatory T cells in antigen-induced arthritis : aggravation of arthritis after depletion and amelioration after transfer of CD 4 + CD 25 + T cells

It is now generally accepted that CD4+CD25+ Treg cells play a major role in the prevention of autoimmunity and pathological immune responses. Their involvement in the pathogenesis of chronic arthritis is controversial, however, and so we examined their role in experimental antigen-induced arthritis in mice. Depletion of CD25-expressing cells in immunized animals before arthritis induction led to increased cellular and humoral immune responses to the inducing antigen (methylated bovine serum albumin; mBSA) and autoantigens, and to an exacerbation of arthritis, as indicated by clinical (knee joint swelling) and histological scores. Transfer of CD4+CD25+ cells into immunized mice at the time of induction of antigen-induced arthritis decreased the severity of disease but was not able to cure established arthritis. No significant changes in mBSAspecific immune responses were detected. In vivo migration studies showed a preferential accumulation of CD4+CD25+ cells in the inflamed joint as compared with CD4+CD25cells. These data imply a significant role for CD4+CD25+ Treg cells in the control of chronic arthritis. However, transferred Treg cells appear to be unable to counteract established acute or chronic inflammation. This is of considerable importance for the timing of Treg cell transfer in potential therapeutic applications.
How much of the invader's genetic variability can slip between our fingers? A case study of secondary dispersal of Poa annua on King George Island (Antarctica)

Abstract We studied an invasion of Poa annua on King George Island (Maritime Antarctic). The remoteness of this location, its geographic isolation, and its limited human traffic provided an opportunity to trace the history of an invasion of the species. Poa annua was recorded for the first time at H. Arctowski Polish Antarctic Station in the austral summer of 1985/6. In 2008/9, the species was observed in a new locality at the Ecology Glacier Forefield (1.5 km from “Arctowski”). We used AFLP to analyze the genetic differences among three populations of P. annua: the two mentioned above (Station and Forefield) and the putative origin of the introduction, Warsaw (Poland). There was 38% genetic variance among the populations. Pairwise ФPT was 0.498 between the Forefield and Warsaw populations and 0.283 between Warsaw and Station. There were 15 unique bands in the Warsaw population (frequency from 6% to 100%) and one in the Station/Forefield populations (which appears in all analyzed individuals from both populations). The Δ(K) parameter indicated two groups of samples: Warsaw/Station and Forefield. As indicated by Fu's Fs statistics and an analysis of mismatch distribution, the Forefield population underwent a bottleneck and/or founder effect. The Forefield population was likely introduced by secondary dispersal from the Station population.
Efficacy and Safety of Repeated Samarium-153 Lexidronam Treatment in a Patient with Prostate Cancer and Metastatic Bone Pain

A patient with stage D3 prostate cancer was given 11 separate doses of samarium-153 lexidronam (Sm-153 ethylenediaminetetramethylene phosphonate) of 1 mCi/kg (37 MBq/kg) in a period of 28 months for bone pain from metastases. With the first five doses, Sm-153 lexidronam clearly reduced his bone pain and improved his quality of life, as determined by pain-assessment scores and the patient’s self-assessment of its effect on his ability to perform activities of daily living. With doses 6 through 11, pain at baseline was on average less, and as a result beneficial effects after treatment were not as apparent. Samarium-153 lexidronam produced transient decreases in the leukocyte and platelet counts, but these never became low enough to cause clinical concern. This case shows both the efficacy and the safety of Sm-153 lexidronam in repeated treatments for metastatic bone pain in patients with prostate cancer.
A particle swarm optimization algorithm for beam angle selection in intensity-modulated radiotherapy planning

Automatic beam angle selection is an important but challenging problem for intensity-modulated radiation therapy (IMRT) planning. Though many efforts have been made, it is still not very satisfactory in clinical IMRT practice because of overextensive computation of the inverse problem. In this paper, a new technique named BASPSO (Beam Angle Selection with a Particle Swarm Optimization algorithm) is presented to improve the efficiency of the beam angle optimization problem. Originally developed as a tool for simulating social behaviour, the particle swarm optimization (PSO) algorithm is a relatively new population-based evolutionary optimization technique first introduced by Kennedy and Eberhart in 1995. In the proposed BASPSO, the beam angles are optimized using PSO by treating each beam configuration as a particle (individual), and the beam intensity maps for each beam configuration are optimized using the conjugate gradient (CG) algorithm. These two optimization processes are implemented iteratively. The performance of each individual is evaluated by a fitness value calculated with a physical objective function. A population of these individuals is evolved by cooperation and competition among the individuals themselves through generations. The optimization results of a simulated case with known optimal beam angles and two clinical cases (a prostate case and a head-and-neck case) show that PSO is valid and efficient and can speed up the beam angle optimization process. Furthermore, the performance comparisons based on the preliminary results indicate that, as a whole, the PSO-based algorithm seems to outperform, or at least compete with, the GA-based algorithm in computation time and robustness. In conclusion, the reported work suggested that the introduced PSO algorithm could act as a new promising solution to the beam angle optimization problem and potentially other optimization problems in IMRT, though further studies need to be investigated.
Exon 9 mutations in the WT1 gene, without influencing KTS splice isoforms, are also responsible for Frasier syndrome

We report new mutations in exon 9 of the WT1 gene that did not alter the ratio of +/– KTS splice isoforms in two unrelated patients with Frasier syndrome (FS). The mutation of intron 9 inducing defective alternative splicing was reported to be responsible for this syndrome. The mutations found in our cases occurred in the same exon of the WT1 gene as detected in Denys‐Drash syndrome (DDS) and could not be explained by the previously proposed mechanism. The results suggest that the two syndromes originate from the same WT1 gene abnormality. From a molecular biological point of view, we concluded that the two diseases were not separable, and that FS should be included as an atypical form of DDS. Hum Mutat 14:466–470, 1999. © 1999 Wiley‐Liss, Inc.
Communication fault injection for multi-protocol Java applications testing

Network applications with high dependability requirements must be carefully tested under communication faults to enhance confidence in proper behavior. Fault injection is very useful for these tests. When the applications use more than one protocol, such as UDP, TCP and RMI, a suitable tool that properly handles all of them is required. However, existing tools either are unable to test this kind of application or impose relevant drawbacks. This paper presents Comform, a communication fault injector for multi-protocol Java applications. It intercepts protocol messages at JVM level and uses firewall rules for fault emulation. The approach is useful for both white and black box testing and preserves the target's source code.
The familial aggregation of obstructive sleep apnea.

An inherited basis for sleep-disordered breathing (SDB) has been suggested by reports of families with multiple affected members and by a previous study of the familial aggregation of symptoms of SDB. In this study, we quantify and characterize the aggregation of SDB and assess the degree to which familial similarities may be independent of obesity. This was a genetic-epidemiologic study that assessed the distribution of SDB in families identified through a proband with diagnosed sleep apnea and among families in the same community with no relative with known sleep apnea. SDB was assessed with overnight in-home monitoring of airflow, oxygen saturation, chest wall impedance, heart rate, and body movement. Standardized questionnaires were used to assess symptoms, and weight, height, and neck circumference were measured directly. Intergenerational and intragenerational correlation coefficients and pairwise odds ratios (ORs) were calculated with adjustment for proband sampling. In toto, 561 members of 91 families were studied: (1) 47 subjects with laboratory-confirmed SDB (index probands), (2) 44 community control subjects, and (3) the spouses and relatives of 1 and 2. Of all 91 families, 32 (35%) had two or more members with SDB, 30 (33%) had one affected member, and 29 had no affected members. SDB was more prevalent in the relatives of index probands (21%) than among neighborhood control subjects (12%) (p = 0.02). (ABSTRACT TRUNCATED AT 250 WORDS)
Suckling mouse cataract agent (SMCA) in mice. I. Factors affecting the incidence of cataracts and growth of virus in several strains of mice.

Summary SMCA virus induces cataracts in a high percentage of infected suckling mice. Maximal SMCA-induced cataract rates were obtained only when virus doses of 10 4.0 ELD 50 or greater were inoculated intracerebrally into suckling mice 4 days of age or younger. Virus inoculated by the intravenous or intraperitoneal routes did not produce cataracts. The SMCA-induced cataract rate was mouse strain-dependent. Cataract rates, based on eye examination at age 30 days, varied from 85% in strain C57B1/6Ha mice to 3% in strain A mice. After 30 days, rates decreased in most mouse strains, but in strain A mice the cataract rate gradually increased to a rate of 44% at 1 year (late cataract strain). Comparative virus assays were performed of the brains, liver-spleen tissues and eyes of SMCA-inoculated strain CFW(A) (30-day cataract rate 46%) and strain A (30-day cataract rate 3%) mice. In each mouse strain virus reached peak titers in all tissues studied in 7 to 15 days. Virus titers then slowly decreased, disappearing from liver-spleen tissues and most eyes by 60 days, but persisting indefinitely (up to 827 days) in the brain. Eye infection rates were similar (88% in A mice, 91% in CFW(A) mice) in both strains of mice. However, in the late cataract strain A mice, virus clearing from eyes and viscera occurred earlier, and peak titers of virus in eyes were lower than in CFW(A) mice.
Radiation Studies of Spin-Transfer Torque Materials and Devices

Spin-transfer torque film stacks and devices having in-plane magnetization were irradiated using a cobalt-60 gamma source. Samples were also exposed to 2 MeV and 220 MeV protons. Measurements of magnetization vs. field, ferromagnetic resonance, and tunnel magnetoresistance were performed on the film stacks before and after exposure to these sources and no changes were observed in the associated material properties. Spin-transfer torque devices were exposed to the same sources and show no changes in bit-state or write performance.
Involvement of Gaba and Cannabinoid Receptors in Central Food Intake Regulation in Neonatal Layer Chicks: Role of CB1 and Gabaa Receptors

Feeding behavior is regulated via a complex network which interacts via diverse signals from central and peripheral tissues. Endocannabinoids modulate release of GABA in a variety of regions of the central nervous system. Endocannabinoids and GABAergic system have an important role in the central regulation of appetite. Thus, the present study examines the possible interaction of central canabinoidergic and GABAergic systems on food intake in 3-h food-deprived (FD3) neonatal layer-type chicks. The results of this study showed that intracerebroventricular (ICV) injection of 2-AG (2-Arachidonoylglycerol, selective CB1 receptors agonist, 2μg) significantly increased food intake and this effect of 2-AG was attenuated by Picrotoxin (GABAA antagonist, 0.5μg) (P<0.001); but 21ng CGP54626 (GABAB antagonist) had no effect (p>0.05). Also, hyperphagic effect of CB65 (CB2 receptors agonist, 1.25μg) was not affected by Picrotoxin or CGP54626 (p>0.05). Moreover, the food intake of chicks was significantly increased by ICV injection of GABAA agonist (Gaboxadol, 0.2 μg) and SR141716A (CB1 receptors antagonist, 6.25μg) significantly decreased Gaboxadol-induced hyperphagia (P<0.001) but CB2 receptors antagonist (AM630, 1.25μg) had no effect. In contrast, co-injection of SR141716A or AM630 with GABAB agonist (baclofen, 0.2μg) had no effect on the hyperphagia induced by baclofen (p>0.05). These data showed there might be an interaction between central cannabinoidergic and GABAergic systems via CB1 and GABAA receptors in control of food intake in neonatal layer chicks.
Spectroscopic and Calorimetric Approach to Understand the Molecular Basis of Self-Association of Aureolic Acid Antibiotic, Chromomycin A3

Chromomycin A3 (CHR, pKa = 7.0), an aureolic acid group of antitumor antibiotic, undergoes self-association in aqueous solution in neutral and anionic forms. Self-association processes of neutral and anionic CHR have been studied in pH 5.0 and pH 9.0, respectively using different spectroscopic methods such as absorbance, fluorescence, CD, NMR and isothermal titration calorimetry (ITC). Results from these studies reveal that at low concentration (2 + CHR (CHR)3 and (CHR)3 + CHR (CHR)4. Analysis of NMR spectra of 100 μM and 1 mM CHR indicates that the self-association of CHR (neutral and anionic form) is most likely to happen via hydrophobic interaction involving the sugar moieties and surrounding water molecules. Calorimetric studies indicate that self-association of both anionic and neutral CHR is entropy driven. These observations imply that sugar substituents play a major role in their state of aggregation after biosynthesis from a gene cluster. The self-association features of the antibiotic have been compared with those of Mithramycin, an antibiotic of the same group.
Female adnexal tumor of probable wolffian origin: a clinicopathological case report and a possible new treatment

Female adnexal tumors of probable wolffian origin (FATWOs) are rare tumors arising in the broad ligament from the remnants of the mesonephric duct. We report a case of recurrent disease. A 15-year-old girl who presented with a painful pelvic mass underwent a laparotomy with tumor resection. Pathology findings confirmed a FATWO. The tumor recurred within 2 years and was treated with multiple chemotherapy regimens, including a platinum-based drug, and surgery for progressive disease. The tumor was positive for c-kit oncogene (CD 117). Gleevac therapy, a tyrosine kinase inhibitor, was prescribed, and she developed severe persistent lower abdominal pain 2 months later. She underwent a hysterectomy and debulking of retroperitoneal masses. Pathology showed evidence of tumor necrosis, suggesting a possible beneficial effect, and she was recommenced on Gleevac in an effort to prevent recurrences. She is currently asymptomatic, without evidence of disease 10 months after surgery, continuing on Gleevac therapy. FATWOs are very rare tumors. Most cases are benign but have the potential to recur and metastasize. There is limited knowledge about the optimal treatment for this neoplasm. Our patient's favorable response to Gleevac therapy supports the concept of targeted molecular therapy in patients with c-kit-positive FATWO tumors.
Objective antitumor activity of acivicin in patients with recurrent CNS malignancies: a Southwest Oncology Group trial.

Acivicin (AT-125) is a glutamine antagonist with dose-limiting, schedule-dependent CNS toxicity and predictable CSF penetration after intravenous administration. Because of these properties, a trial in CNS malignancies was initiated. Thirty-two patients with recurrent or residual malignant astrocytomas were treated with AT-125. The majority of patients had glioblastoma multiforme (24) and had received prior nitrosoureas (21). The median age was 50 years, and Southwest Oncology Group (SWOG) performance status was 2. The major determinant of response was based upon radiologic criteria using computed tomographic (CT) scanning and/or magnetic resonance imaging (MRI) scans. The tumor mass was measured in two perpendicular planes, which yielded the largest cross-sectional area. Standard solid tumor criteria for response were used. All responding patients also had a stable or tapered dose of corticosteroids with stable or improved performance status and neurologic examination. There were four objective responses (12%): one complete remission (3 1/2+ years) and three partial remissions (57, 86, and 322 days). Two patients had improvement in disease that did not meet requirements for a partial remission. Toxicity was mild and primarily consisted of nausea, vomiting, and lethargy. Two patients were removed from study due to neurotoxicity (depression and hallucinations). The strict response criteria used in this trial were not those that have been used in testing other active agents such as carmustine (BCNU). We conclude that AT-125 has objective antitumor activity in malignant astrocytomas and warrants further study.
Secondary Bonding Interactions in Some Dichloroanilinium Chlorides

Of the six structures presented here, five involve clearly defined hydrophilic layers built up from classical hydrogen bonding systems. Of three solvent-free structures, 2,4- and 3,5-dichloroanilinium chlorides both form ribbon structures involving annelated R24 (8) rings with NH2 donors (two hydrogen atoms from the positively charged NH3 groups) and chloride acceptors. The ribbons are linked by weaker interactions to form layers. 2,5-Dichloroanilinium chloride forms a layer structure directly, with rings R36 (12) exactly analogous to those previously observed in 2-chloroanilinium chloride. 2,6-Dichloroanilinium chloride methanol solvate forms a different type of ribbon structure, with alternating R24 (8) and R46 12) rings; the latter involve two chlorides, two NH2 groups and two methanols. These ribbons too are linked to form layers. 2,3-Dichloroanilinium chloride hydrate forms layers with two types of ring R35 (10); one involves two NH2, two chlorides and the OH part of a water, whereas in the other, an NH2 is replaced by OH2. In all these structures the aromatic groups project approximately perpendicular to the layers to form hydrophobic regions; for all except 3,5-dichloroanilinium chloride, neighbouring layers are linked by weaker interactions such as C-H···Cl hydrogen bonds or Cl···Cl contacts. The final structure, 3,5-dichloroanilinium chloride 1/4-hydrate, is completely different; it involves two types of columns, one built up from quadrilaterals of Cl···Cl contacts between cations and the other consisting of “nanotubes ’ of NH3 groups and chloride anions linked by two- and three-centre hydrogen bonds. The columns are in turn linked by cation-anion Cl···Cl interactions.