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The magnetic properties of the two isostructural molecule-based magnets, Ni(NCS)$_{2}$(thiourea)$_{2}$, $S$ = 1, [thiourea = SC(NH$_2$)$_2$] and Co(NCS)$_{2}$(thiourea)$_{2}$, $S$ = 3/2, are characterised using several techniques in order to rationalise their relationship with structural parameters and ascertain magnetic changes caused by substitution of the spin. Zero-field heat capacity and muon-spin relaxation measurements reveal low-temperature long-range ordering in both compounds, in addition to Ising-like ($D < 0$) single-ion anisotropy ($D_{\rm{Co}} \sim$ -100 K, $D_{\rm{Ni}} \sim$ -10 K). Crystal and electronic structure, combined with DC-field magnetometry, affirm highly quasi-one-dimensional behaviour, with ferromagnetic intrachain exchange interactions $J_{\rm{Co}}\approx+4$ K and $J_{\rm{Ni}}\sim+100$ K and weak antiferromagnetic interchain exchange, on the order of $J'$ $\sim-0.1$ K. Electron charge and spin-density mapping reveals through-space exchange as a mechanism to explain the large discrepancy in $J$-values despite, from a structural perspective, the highly similar exchange pathways in both materials. Both species can be compared to the similar compounds $M$Cl$_2$(thiourea)$_4$, $M$ = Ni(II) (DTN) and Co(II) (DTC), where DTN is know to harbour two magnetic field-induced quantum critical points. Direct comparison of DTN and DTC with the compounds studied here shows that substituting the halide Cl$^-$ ion, for the NCS$^-$ ion, results in a dramatic change in both the structural and magnetic properties., Main text: 13 pages - 11 figures, 2 tables. Supplemental information: 6 pages - 2 figures, 6 tables

We report the results of a muon-spin relaxation (mu SR) investigation of La2-xSrxCoO4, an antiferromagnetic insulating series which has been shown to support charge ordered and magnetic stripe phases and an hourglass magnetic excitation spectrum. We present a revised magnetic phase diagram, which shows that the suppression of the magnetic ordering temperature is highly sensitive to small concentrations of holes. Distinct behavior within an intermediate x range (0.2

© 2016 Williams et al. Background: The presence of population structure in a sample may confound the search for important genetic loci associated with disease. Our four samples in the Family Investigation of Nephropathy and Diabetes (FIND), European Americans, Mexican Americans, African Americans, and American Indians are part of a genome- wide association study in which population structure might be particularly important. We therefore decided to study in detail one component of this, individual genetic ancestry (IGA). From SNPs present on the Affymetrix 6.0 Human SNP array, we identified 3 sets of ancestry informative markers (AIMs), each maximized for the information in one the three contrasts among ancestral populations: Europeans (HAPMAP, CEU), Africans (HAPMAP, YRI and LWK), and Native Americans (full heritage Pima Indians). We estimate IGA and present an algorithm for their standard errors, compare IGA to principal components, emphasize the importance of balancing information in the ancestry informative markers (AIMs), and test the association of IGA with diabetic nephropathy in the combined sample. Results: A fixed parental allele maximum likelihood algorithm was applied to the FIND to estimate IGA in four samples: 869 American Indians; 1385 African Americans; 1451 Mexican Americans; and 826 European Americans. When the information in the AIMs is unbalanced, the estimates are incorrect with large error. Individual genetic admixture is highly correlated with principle components for capturing population structure. It takes ~700 SNPs to reduce the average standard error of individual admixture below 0.01. When the samples are combined, the resulting population structure creates associations between IGA and diabetic nephropathy. Conclusions: The identified set of AIMs, which include American Indian parental allele frequencies, may be particularly useful for estimating genetic admixture in populations from the Americas. Failure to balance information in maximum likelihood, poly-ancestry models creates biased estimates of individual admixture with large error. This also occurs when estimating IGA using the Bayesian clustering method as implemented in the program STRUCTURE. Odds ratios for the associations of IGA with disease are consistent with what is known about the incidence and prevalence of diabetic nephropathy in these populations.

A carefully taken history and thorough physical examination remain the most crucial aspects of diagnosing rheumatic disorders. Non-rheumatologic conditions also need to be kept in mind. Laboratory tests should be looked on as mostly supportive or confirmatory, because many of the tests are relatively nonspecific and may lack sensitivity. If their limitations are recognized, however, the tests can be invaluable tools when the clinician confronts the task of differentiating an array of rheumatologic disorders.

Previous studies suggest a potential association between human immunoglobulin (Ig) genes and susceptibility to systemic lupus erythematosus (SLE). Ig allotypic determinants seem to confer an increased risk for the disease in various ethnic patient populations. In this study we have examined the pattern of restriction fragment length polymorphisms (RFLP) of constant region lambda (Cλ) light chain genes in a group of 78 Venezuelan patients with SLE and 70 healthy controls. The frequency of the 8-kb allele and the 8/8 genotype was significantly lower in normal Venezuelan controls as compared to healthy British Cauca sians ( P = 0.0002 and 0.0007 respectively). In turn, Venezuelan controls showed a higher frequency of the 18-kb allele and the 18/18 genotype ( P = 0.0002 and 0.0052 respectively). However, there were no statistically significant differences in either parameter between Venezuelan SLE patients and healthy controls. Our study argues against a role for lambda light chain constant region genes in predisposition to SLE.

Several approaches have been directed at identifying accurate parameters for the measurement of disease activity in autoimmune disorders, both in humans and in experimental animal models. A great deal of previous effort has focused on determining what constitutes antigenic epitopes on various autologous proteins or tissue components, which then can generate an immune response in the host. Much of this work has been clouded by the fact that normal subjects (both animal and human) seem to mount an immune response to myriad autologous proteins, characterized by the formation of antibodies known as natural autoantibodies. During the course of certain autoimmune diseases such as systemic lupus erythematosus (SLE) or Wegener's granulomatosis (WG), patients produce what appear to be autoantibodies reacting with autologous components such as DNA and Sm antigen (SLE) or proteinase-3 (WG). Low levels of these same autoantibodies are present in IgG derived from normal subjects. Recently, we have found that IgG anti-F(ab')2 from normal subjects, affinity-purified from immunoabsorbent columns of human F(ab_)2 Sepharose, exhibits not only anti-F(ab')2 but also anti-dsDNA and anti-Sm activity. These antibodies constitute an average of 0.02% of normal serum IgG. Similar findings have also been observed in SLE patients with active disease. Our findings suggest that perturbation of the idiotypic network may represent an important fundamental aspect of many autoimmune disorders.

Rheumatoid arthritis (RA) was one of the first systemic disorders to be considered an autoimmune disease. Two major aspects of RA suggest a fundamental immune-mediated derangement in the disease: (1) presence of often massive lymphocytic infiltrates and activated CD4(+) T cells within the inflamed hypertrophied synovium, and (2) production of large amounts of rheumatoid factor (RF) by B-cells and plasma cells in the involved synovium itself. The actual tissue damage to joints and extra-articular structures affected by the disease comes from the rheumatoid inflammatory pannus or granulomatous collections of cells called rheumatoid nodules. RF production has long been studied as a prime example of apparent autoantibody production in association with the basic underlying disease process. RA patients who belong to subtype HLA DR4, Dw4 (DR B1 or 0401, Dw14 (0404/0408), or Dw15 (0405/0410) are most likely to be seropositive for RF and to have severe progressive disease. RFs are felt to represent an autoantibody associated with RA, since they show principal specificity for structures on the Cγ3 and C γ2 (Fc) domains of IgG. Recent work by our group has defined a number of solvent-exposed linear RF-reactive epitopes on Cγ3 and Cγ2 using a strategy of overlapping 7-mers of primary sequence. RFs also have been demonstrated to react with two different regions, SKDWSFY and LSQPKIVKWDR, on β2-microglobulin (β 2m). Many of the RF-reactive sites on Cγ2 and C γ3 as well as on β2m show common immunodominant valines, leucines, tryptophanes, arginines, lysines, and glutamines, thus comprising common reactive residues. In the future, this approach may provide more direct insight into the specificities of other autoantibodies.

Human rheumatoid factors are antibodies of IgG, IgA, or IgM class that show reactions with antigenic determinants present on other immunoglobulin molecules. The most commonly measured rheumatoid factor relates to the 19S IgM type, which reacts by agglutination of latex particles coated with 7S IgG and is often measured in the standard latex fixation test. Approximately 65 to 70 per cent of patients with rheumatoid arthritis show positive serologic tests for rheumatoid factor; however, a number of other chronic disease conditions are also associated with positive rheumatoid factor reactions, including infective endocarditis, sarcoidosis, leprosy, and other hyperglobulinemic conditions. Although extensive serologic and immunochemical studies have identified a number of specific antigenic structural sites on immunoglobulin molecules that react with rheumatoid factors, recent studies have shown that a certain proportion of such antibodies may show cross-reactivity with DNA-histone complexes as well. It is still not entirely clear how rheumatoid factors fit into the pathogenesis of rheumatoid arthritis itself.

Opacification of the rabbit lens was studied as a function of dose and time post irradiation for single and fractionated doses of 1 MeV X-rays, 20 and 100 MeV protons. The degree of opacification was found to be a function of time, radiation dose, LET and mode of dose deliverance. Fractionation reduced the final degree of lens opacification by a factor of 2 or less, depending upon the dose and type of radiation.

The amino-terminal amino-acid sequence has been determined for the kappa light chains of nine IgM cold agglutinins with specificity for blood group-related carbohydrate antigens. Six of the nine sequences corresponded to the prototype VK III subgroup pattern, two to that of subgroup VK II , and only one to the VK I subgroup. This distribution of kappa subgroups differs markedly from that of normal and myeloma proteins sequenced to date, where the VK I subgroup is more prevalent than either VK II or VK III . Evidence is presented that supports the conclusion that the unusual subgroup distribution relates to the antibody property itself and not to some other attribute of these molecules.

Summary One side of the udder of each of 16 ewes was infused with a polyvalent cell-toxoid vaccine during the dry period. The vaccine contained bacterial cells of several strains including phage type 42D,α-haetnolysin and leucocidin. A dose of 106 organisms of phage type 42D was used to challenge the immunised and non-immunised sides of the udder 3 weeks after lambing. Tiventy-four hours after challenge 5 of the ewes had developed acute mastitis and 7 a mild mastitis of the non-immunised side, but the immunised sides were palpably normal. In 4 ewes there was no evidence of inflammation on either side at this time. Clinical examination one month after challenge revealed that the non-immunised sides were indurated in most of the ewes. During the first 3 days after infection the number of bacteria cultured from milk from the immunised sides was always less than that from the non-immunised sides. Thereafter bacterial counts in milk were sometimes greater in milk from the immunised sides. However, analysis of variance of the results showed that the milk from the immunised sides contained significantly fewer staphylococci than that from the non-immunised sides during the first 14 days after infection. In the majority of the ewes the staphylococcal agglutination titre was higher in milk collected immediately before challenge from the immunised sides. It is suggested that a local immune response to cell wall antigens was largely responsible for the protection observed. Attempts to demonstrate an enhancement of the local response by the addition of 5 μg. of lipopolysaccharide to the vaccine were unsuccessful.

Rheumatoid factors (RF) occur during the course of various infections such as leprosy, infective endocarditis, tuberculosis, trypanosomiasis, visceral larva migrans, infectious mononucleosis, influenza A, hepatitis A or cytomegalovirus. When first described it seemed logical to assume that host-self-immunization with autologous immune complexes provided the initial stimulus for RF production. Subsequently extensive characterization of bacterial, parasitic and viral Fc receptors has suggested an alternative explanation for rheumatoid factor associated with infections. It seems possible that patients make an initial immune response to infecting agent Fc receptors and that anti-anti-Fc receptors or anti-idiotypes either then directly stimulate rheumatoid factor production or are themselves rheumatoid factors. Such a hypothesis might also be applied to rheumatoid arthritis itself where either infecting agent or autologous cell Fc receptors could be the initial immunizing epitopes involved in rheumatoid factor production.

Opacification of the rabbit lens was studied as a function of dose and time after irradiation with 1 MeV X-rays, 20 and 100 MeV protons. The degree of opacification was dependent upon time, radiation dose and LET. Twenty MeV protons produced the greatest relative lens damage. The relative biological effectiveness (RBE) was determined for the 20 and 100 MeV protons relative to 1 MeV X-ray induced lens changes. The RBE was found to increase with LET.