Modulating troubles affiliating in initial interactions:The role of remedial accounts

Much of the research on affiliation to date has focused on how people do (dis)affiliation. This paper explores the remedial work that follows instances of disaffiliation between interactants who are getting acquainted. Building on an interactional pragmatics analytical approach informed by methods and research in conversation analysis, findings indicate that extended remedial accounts recurrently follow moments of disaffiliation in initial interactions. These remedial accounts enable participants to reposition a prior disaffiliative stance as (ostensibly) affiliative. It appears in initial interactions, then, that remedial accounts play an important role in modulating troubles in affiliating. We propose that the considerable interactional work undertaken by these participants to modulate such troubles reflects a general preference for agreeability in initial interactions, at least amongst (Australian and British) speakers of English

Allosteric p97 inhibitors can overcome resistance to ATP-competitive p97 inhibitors for potential anti-cancer therapy

A major challenge of targeted cancer therapy is the selection for drug‐resistant mutations in tumor cells leading to loss of treatment effectiveness. p97/VCP is a central regulator of protein homeostasis and a promising anti‐cancer target because of its vital role in cell growth and survival. One ATP‐competitive p97 inhibitor, CB‐5083, has entered clinical trials. Selective pressure on HCT116 cells treated with CB‐5083 identified 5 different resistant mutants. Identification of p97 inhibitors with different mechanisms of action would offer the potential to overcome this class of resistance mutations. Our results demonstrate that two CB‐5083 resistant p97 mutants, N660K and T688A, were also resistant to several other ATP‐competitive p97 inhibitors, whereas inhibition by two allosteric p97 inhibitors NMS‐873 and UPCDC‐30245 were unaffected by these mutations. We also established a CB‐5083 resistant cell line that harbors a new p97 double mutation (D649A/T688A). While CB‐5083, NMS‐873, and UPCDC‐30245 all effectively inhibited proliferation of the parental HCT116 cell line, NMS‐873 and UPCDC‐30245 were 30‐fold more potent than CB‐5083 in inhibiting the CB‐5083 resistant D649A/T688A double mutant. Our results suggest that allosteric p97 inhibitors are promising alternatives when resistance to ATP‐competitive p97 inhibitors arises during anti‐cancer treatment

Jimmy Carter and the rise of the New Christian Right.

This thesis will extend the current re-evaluation of the presidency of Jimmy Carter through a detailed examination of the enduring impact of his Southern Baptist Christian faith upon the modern American political discourse. It will show that the relationship between Jimmy Carter's deeply felt religiosity and his political vision is primary to an understanding of the lasting legacy of his presidency. Carter dramatically reconfigured the relationship between religious faith and the presidency. The first president to articulate forthrightly a highly intimate and deeply felt personal religious faith to the American electorate, Carter placed spiritual concerns at the centre of the American political debate. I will investigate Carter's relationship with the forces of conservative Christendom with regards to a number of interwoven policy issues deemed by the evangelical community to be emblematic of the increasingly liberal, secular humanist nature of the American public and political discourse. Specifically, I will explore the issues of abortion, the role of religion in private schools, the place of prayer in public schools, gay and lesbian rights, Christian family values and the Congressional ratification of the Equal Rights Amendment. I will discuss how the policies of the Carter White House on these so-called 'hot button' issues for religious conservatives acted as a catalyst for Christian political activism during the 1970s, laying the basis for their key role in American political life thereafter. I will explain how, paradoxically, the most overtly evangelical president in American history not only failed to retain the support of the conservative Christian community but was integral in the emergence of the New Religious, or New Christian Right, as a key Republican Party constituency. Jimmy Carter successfully reawakened faith-based politics but because his faith did not exactly mirror the religious and political agenda of the disparate groups that make up the religious conservative movement within the United States, that newly awakened force within American politics ultimately used its power to replace him with Ronald Reagan, a president who more carefully articulated their agenda

Neurofibroma of the ovary

We report an unusual example of ovarian neurofibroma in a woman with neurofibromatosis (von Recklinghausen's disease). The neoplasm caused ovarian enlargement which surgically simulated malignant neoplasm. Ovarian neurofibromas are extremely rare and may arise from small myelinated nerves in the ovarian hilum.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28551/1/0000350.pd

Allosteric p97 inhibitors can overcome resistance to ATP-competitive p97 inhibitors for potential anti-cancer therapy

A major challenge of targeted cancer therapy is the selection for drug‐resistant mutations in tumor cells leading to loss of treatment effectiveness. p97/VCP is a central regulator of protein homeostasis and a promising anti‐cancer target because of its vital role in cell growth and survival. One ATP‐competitive p97 inhibitor, CB‐5083, has entered clinical trials. Selective pressure on HCT116 cells treated with CB‐5083 identified 5 different resistant mutants. Identification of p97 inhibitors with different mechanisms of action would offer the potential to overcome this class of resistance mutations. Our results demonstrate that two CB‐5083 resistant p97 mutants, N660K and T688A, were also resistant to several other ATP‐competitive p97 inhibitors, whereas inhibition by two allosteric p97 inhibitors NMS‐873 and UPCDC‐30245 were unaffected by these mutations. We also established a CB‐5083 resistant cell line that harbors a new p97 double mutation (D649A/T688A). While CB‐5083, NMS‐873, and UPCDC‐30245 all effectively inhibited proliferation of the parental HCT116 cell line, NMS‐873 and UPCDC‐30245 were 30‐fold more potent than CB‐5083 in inhibiting the CB‐5083 resistant D649A/T688A double mutant. Our results suggest that allosteric p97 inhibitors are promising alternatives when resistance to ATP‐competitive p97 inhibitors arises during anti‐cancer treatment

Pneumocystis carinii pneumonia. Cytologic manifestations and rapid diagnosis in routinely prepared papanicolaou-stained preparations

In this study of 28 immunocompromised patients, it was found that Pneumocystis carinii pneumonia could be easily and reliably diagnosed by examination of routinely prepared, Papanicolaou-stained cellular samples obtained by bronchoalveolar lavage, bronchial brushing, and bronchial washing. The distinctive intra-alveolar exudate of pneumocystosis observed in lung biopsy specimens was readily discernible in all of the cellular samples that demonstrated P. carinii by special stains. The exudate was not present in any of the P. carinii-negative samples. Routinely prepared, Papanicolaou-stained cellular samples can be relied upon for the rapid diagnosis of P. carinii pneumonia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25965/1/0000031.pd

Course of FEV1 after Onset of Bronchiolitis Obliterans Syndrome in Lung Transplant Recipients

Rationale: Bronchiolitis obliterans syndrome (BOS), defined by loss of lung function, develops in the majority of lung transplant recipients. However, there is a paucity of information on the subsequent course of lung function in these patients. Objectives: To characterize the course of FEV1 over time after development of BOS and to determine the predictors that influence the rate of functional decline of FEV1. Methods: FEV1% predicted (FEV1%pred) trajectories were studied in 111 lung transplant recipients with BOS by multivariate, linear, mixed-effects statistical models. Measurements and Main Results: FEV1%pred varied over time after BOS onset, with the steepest decline typically seen in the first 6 months (12% decline; p < 0.0001). Bilateral lung transplant recipients had significantly higher FEV1%pred at BOS diagnosis (71 vs. 47%; p < 0.0001) and at 24 months after BOS onset (58 vs. 41%; p = 0.0001). Female gender and pretransplant diagnosis of idiopathic pulmonary fibrosis were associated with a steeper decline in FEV1%pred in the first 6 months after BOS diagnosis (p = 0.02 and 0.04, respectively). A fall in FEV1 greater than 20% in the 6 months preceding BOS (termed “rapid onset”) was associated with shorter time to BOS onset (p = 0.01), lower FEV1%pred at BOS onset (p < 0.0001), steeper decline in the first 6 months (p = 0.03), and lower FEV1%pred at 2 years after onset (p = 0.0002). Conclusions: Rapid onset of BOS, female gender, pretransplant diagnosis of idiopathic pulmonary fibrosis, and single-lung transplantation are associated with worse pulmonary function after BOS onset.Supported in part by National Institutes of Health grants K23 HL077719 (V.N.L.) and K24 HL04212 (F.J.M.), and by a grant from the American Society of Transplantation/ Chest Foundation (V.N.L.).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91969/1/2007 AJRCCM Course of FEV1 after Onset of Bronchiolitis Obliterans Syndrome in Lung Transplant Recipients.pd

Alveolar soft part sarcoma of the uterine cervix

Alveolar soft part sarcoma is a histologically distinctive neoplasm of uncertain histogenesis. Since its initial description in 1952, more than 200 cases have been reported. The extremities are most often the sites of involvement; the tongue, bones, and the orbit have been less commonly involved. The present paper describes a case of alveolar soft part sarcoma which was present only within the uterine cervix of a 37-year-old woman. Histologically, the tumor cells were arranged in the characteristic alveolar pattern; diagnostic PAS-positive diastase-resistant needle-shaped crystals were observed within the cytoplasm of the tumor cells. After the initial biopsy, the patient underwent a radical hysterectomy and pelvic lymph node dissection. Although no residual tumor was found within the cervix, a microscopic focus of tumor was detected in an obturator lymph node. The patient is at present clinically free of disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25551/1/0000093.pd