CD4+ cytolytic effectors are inefficient in the clearance of Listeria monocytogenes

Cytotoxic T lymphocytes (CTL) recognize and lyse target cells through the interaction of the T-cell receptor complex with the class I or class II major histocompatibility complex (MHC). The production of class I-restricted CTL has been shown to be critical to the elimination of specific pathogens including . However, the function of class II-restricted CTL in the clearance of intracellular pathogens is poorly understood. H-2β-microglobulin-deficient mice (βM−/−) are not able to produce CD8 CTL in response to infection with . We used this model to evaluate the efficacy of class II-restricted CTL, in the absence of a class I-restricted response, during a primary infection with . We demonstrate that, despite their effectiveness in adoptive transfer of protection, -specific CD4 class II-restricted cytotoxic lymphocytes are ineffective in decreasing titres of in the spleen after an established infection. In βM−/− mice, persistence of in the spleen was found preferentially in class II-negative cells. Surprisingly, class I-restricted CTL from C57BL/6 mice were capable of decreasing bacterial titres during an established infection even in the absence of detectable class I on the surface of cells from βM−/− mice. These data strongly suggest that, in the absence of a class I-restricted response, pathogens that elicit a class II-restricted cytotoxic response may escape prompt eradication by the immune system

Quantitation of Aortic Valvular Insufficiency Using Radioactive Tracers: An Experimental Study In Vitro

A method has been developed in vitro for quantitation of aortic valvular insufficiency (Al) based on the use of ladioactive traceis lo genei-ate graphic recordings of the movement of blood out of the ventricle and back again. The regurgitant fraction of stroke volume (peirent of Al) is read from this recording. The method was evaluated in a mechanical heart model by comparing Al values read from the istope recordings and Al values determined volumetrically. The recordings gave excellent agreement with the volumetric results (Corr. Coeff. .9). These in vitro results are of such quality that clinical trials seem justified

Validation of the Harvard Lyman-α in situ water vapor instrument: Implications for the mechanisms that control stratospheric water vapor

Building on previously published details of the laboratory calibrations of the Harvard Lyman-α photofragment fluorescence hygrometer (HWV) on the NASA ER-2 and WB-57 aircraft, we describe here the validation process for HWV, which includes laboratory calibrations and intercomparisons with other Harvard water vapor instruments at water vapor mixing ratios from 0 to 10 ppmv, followed by in-flight intercomparisons with the same Harvard hygrometers. The observed agreement exhibited in the laboratory and during intercomparisons helps corroborate the accuracy of HWV. In light of the validated accuracy of HWV, we present and evaluate a series of intercomparisons with satellite and balloon borne water vapor instruments made from the upper troposphere to the lower stratosphere in the tropics and midlatitudes. Whether on the NASA ER-2 or WB-57 aircraft, HWV has consistently measured about 1–1.5 ppmv higher than the balloon-borne NOAA/ESRL/GMD frost point hygrometer (CMDL), the NOAA Cryogenic Frost point Hygrometer (CFH), and the Microwave Limb Sounder (MLS) on the Aura satellite in regions of the atmosphere where water vapor is <10 ppmv. Comparisons in the tropics with the Halogen Occultation Experiment (HALOE) on the Upper Atmosphere Research Satellite show large variable differences near the tropopause that converge to ~10% above 460 K, with HWV higher. Results we show from the Aqua Validation and Intercomparison Experiment (AquaVIT) at the AIDA chamber in Karlsruhe do not reflect the observed in-flight differences. We illustrate that the interpretation of the results of comparisons between modeled and measured representations of the seasonal cycle of water entering the lower tropical stratosphere is dictated by which data set is used

Rapid identification of BCR/ABL1-like acute lymphoblastic leukaemia patients using a predictive statistical model based on quantitative real time-polymerase chain reaction: clinical, prognostic and therapeutic implications.

BCR/ABL1-like acute lymphoblastic leukaemia (ALL) is a subgroup of B-lineage acute lymphoblastic leukaemia that occurs within cases without recurrent molecular rearrangements. Gene expression profiling (GEP) can identify these cases but it is expensive and not widely available. Using GEP, we identified 10 genes specifically overexpressed by BCR/ABL1-like ALL cases and used their expression values - assessed by quantitative real time-polymerase chain reaction (Q-RT-PCR) in 26 BCR/ABL1-like and 26 non-BCR/ABL1-like cases to build a statistical "BCR/ABL1-like predictor", for the identification of BCR/ABL1-like cases. By screening 142 B-lineage ALL patients with the "BCR/ABL1-like predictor", we identified 28/142 BCR/ABL1-like patients (19·7%). Overall, BCR/ABL1-like cases were enriched in JAK/STAT mutations (P < 0·001), IKZF1 deletions (P < 0·001) and rearrangements involving cytokine receptors and tyrosine kinases (P = 0·001), thus corroborating the validity of the prediction. Clinically, the BCR/ABL1-like cases identified by the BCR/ABL1-like predictor achieved a lower rate of complete remission (P = 0·014) and a worse event-free survival (P = 0·0009) compared to non-BCR/ABL1-like ALL. Consistently, primary cells from BCR/ABL1-like cases responded in vitro to ponatinib. We propose a simple tool based on Q-RT-PCR and a statistical model that is capable of easily, quickly and reliably identifying BCR/ABL1-like ALL cases at diagnosis

Superconducting Fluxon Pumps and Lenses

We study stochastic transport of fluxons in superconductors by alternating current (AC) rectification. Our simulated system provides a fluxon pump, "lens", or fluxon "rectifier" because the applied electrical AC is transformed into a net DC motion of fluxons. Thermal fluctuations and the asymmetry of the ratchet channel walls induce this "diode" effect, which can have important applications in devices, like SQUID magnetometers, and for fluxon optics, including convex and concave fluxon lenses. Certain features are unique to this novel two-dimensional (2D) geometric pump, and different from the previously studied 1D ratchets.Comment: Phys. Rev. Lett. 83, in press (1999); 4 pages, 5 .gif figures; figures also available at http://www-personal.engin.umich.edu/~nori/ratche

Public health engagement: detection of suspicious skin lesions, screening and referral behaviour of UK based chiropractors.

BACKGROUND: UK morbidity and mortality rates from skin cancer are increasing despite existing preventative strategies involving education and early detection. Manual therapists are ideally placed to support these goals as they see greater quantities of exposed patient skin more often than most other healthcare professionals. The purpose of this study therefore was to ascertain the ability of manual therapists to detect, screen and refer suspicious skin lesions. METHOD: A web-based questionnaire and quiz was used in a sample of UK chiropractic student clinicians and registered chiropractors to gather data during 2011 concerning skin screening and referral behaviors for suspicious skin lesions. RESULTS: A total of 120 questionnaires were included. Eighty one percent of participants agreed that screening for suspicious skin lesions was part of their clinical role, with nearly all (94%) assessing their patients for lesions during examination. Over 90% of the participants reported regularly having the opportunity for skin examination; with nearly all (98%) agreeing they would refer patients with suspicious skin lesions to a medical practitioner. A third of respondents had referred a total of 80 suspicious lesions within the last 12 months with 67% warranting further investigation. CONCLUSIONS: Nearly all respondents agreed that screening patients for suspicious skin lesions was part of their clinical role, with a significant number already referring patients with lesions

Relativity principles in 1+1 dimensions and differential aging reversal

We study the behavior of clocks in 1+1 spacetime assuming the relativity principle, the principle of constancy of the speed of light and the clock hypothesis. These requirements are satisfied by a class of Finslerian theories parametrized by a real coefficient $\beta$, special relativity being recovered for $\beta=0$. The effect of differential aging is studied for the different values of $\beta$. Below the critical values $|\beta| =1/c$ the differential aging has the usual direction - after a round trip the accelerated observer returns younger than the twin at rest in the inertial frame - while above the critical values the differential aging changes sign. The non-relativistic case is treated by introducing a formal analogy with thermodynamics.Comment: 12 pages, no figures. Previous title "Parity violating terms in clocks' behavior and differential aging reversal". v2: shortened introduction, some sections removed, pointed out the relation with Finsler metrics. Submitted to Found. Phys. Let

Novel, bilateral, two-bellied muscles span the extensor forearm, thenar eminence to insert on the proximal phalanx of the thumb: clinical and embryological significance

Muscle and tendon variations in the forearm, wrist and hand are commonly reported in the anatomical and surgical literature. They are frequently the source of inflammatory conditions such as de Quervain’s tenosynovitis or carpal tunnel syndrome. During academic dissection, a cadaver presented with bilateral, additional muscles running parallel to the abductor pollicis longus muscles (APL) in the extensor compartment of the forearm. Both additional muscles had two bellies, one proximal and one distal, with an intervening tendon. The proximal bellies were separate and distinct from the adjacent APLs. The tendons traversed the first dorsal compartments with the tendons of the APLs and the extensor pollicis brevis muscles (EPB). The distal bellies lay adjacent to the abductor pollicis brevis (APB) muscles in the thenar compartments, and inserted onto the volar base of the proximal phalanges of the thumbs. Following a thorough search of the literature, we determined that these additional muscles constitute a previously unreported variation. This report details the variation, compares it with other reported variations, presents the related embryology, and reviews the significance of this variation as it relates to inflammatory conditions and surgical procedures

Simultaneous, in situ measurements of OH, HO_2, O_3, and H_2O: A test of modeled stratospheric HO_x chemistry

Simultaneous, in situ measurements of OH, HO_2, H_2O, and O_3 from 37–23 km are reported. The partitioning between OH and HO_2 and the total HO_x concentration are compared with expected steady-state values. The ratio of HO_2 to OH varies from less than 2 at 36 km to more than 3 at 25 km; in the lower stratosphere this ratio is nearly a factor of two less than predicted. The data are used to calculate HO_x production and loss rates. The measured HOx mixing ratio is consistent with production dominated by the reaction of O(1D) with H_2O, and loss controlled by NO_y below 28 km and HO_x above 30 km. The steady-state concentration of H_2O_2 is inferred from the measured HO_2 concentration and calculated photolysis rate. The maximum H_2O_2 mixing ratio (at 33 km) is predicted to be less than 0.2 ppb