Variation in the Thyrotropic Activity of Human Chorionic Gonadotropin in Chinese Hamster Ovary Cells Arises from Differential Expression of the Human Thyrotropin Receptor and Microheterogeneity of the Hormone.

The role of hCG as a stimulator of the human thyroid has been a subject of controversy, because discrepant results have been obtained in different in vitro assays. In an attempt to explain the variation observed in the thyroid response to hCG, we investigated the ability of hCG and that of its isoforms and glycosylation variants to inhibit [125I]bovine (b) TSH binding and stimulate adenylate cyclase in two clones, JP09 and JP26, of Chinese hamster ovary cells stably transfected with the human TSH receptor (hTSHr). The two clones differed with respect to the number of hTSHr expressed per cell (34,000 in JP09 and 2,000 in JP26 cells). Both responded extremely well to bTSH; the cAMP response to 0.001 IU/L bTSH was distinguishable from basal values. Interestingly, JP09 cells were readily stimulated by hCG (20-100 mg/L; 0.52-2.6 x 10(-6) mol/L) to release cAMP, whereas JP26 cells showed little if any response. Also, cAMP stimulation produced by asialo-hCG was 12-fold in JP09 cells and only 4-fold in JP26 cells compared to 45- and 67-fold stimulations by bTSH, respectively. Stimulation by asialo-hCG was approximately 30% that of bTSH in JP09 cells, but less than 6% in JP26 cells. When assessing the thyrotropic activity of the microheterogeneous isoforms of hCG, more alkaline pI forms were found to be more active than those of a more acidic pI regardless of whether they were derived from normal or molar pregnancy urine. Further studies with hCG, asialo-hCG, asialoagalacto-hCG, and deglycosylated hCG revealed that removal of sialic acid caused a marked increase in both its affinity for hTSHr and its cAMP-releasing potency, whereas removal of further carbohydrate, although it slightly enhanced receptor binding, was detrimental to adenylate cyclase activation. In conclusion, differences in hTSHr expression may cause a variation in the cAMP response to hCG or its glycosylation variants, as does the microheterogeneity of the hormone itself. These mechanisms may be responsible at least in part for the divergent responses of different cell types to hCG and render interpretation of the physiological meaning of the data obtained in recombinant receptor systems difficult

Sherman Alexie’s Literary Works as Native American Social Realistic Projections

This paper aims to look at the social realistic issues in the context of Sherman Alexie’s literary works. Alexie is one of the postmodern authors in the United States of America. He is very popular among his Native American society as well as community for representing social reality of his age. This paper is divided into several sections; each section shows a benchmark of the 21st century Social Picture of the Native Americans in the light of Alexian Literary Works. It also scrutinizes stories, and novels with a view to highlighting a faithful picture of Native Americans in the light of everyday social issues, including poverty, alcoholism, unhealthiness, racism, and suicidal act. Basically, the main part of my paper deals with social problems of Native Americans in the United States of America as depicted in Alexie’s literary works. It highlights an awareness of the Native Americans so as to keep themselves aloof from drug addiction, poverty, depression, and psychological trauma. Here I have also applied the critical theory of Social Realism with a view to unveiling a subtle literary affinity with Alexie’s works. In this study, I would like to show the significance of this study, and research methodology as well

The Impact of Leverage Variances on Growth: A Longitudinal Study of Pakistan’s Corporate Sector

This study is an empirical investigation into the impact of leverage deviations from the target on growth of companies listed on the Karachi Stock Exchange (KSE). It is posited that leverage variance impedes the growth of firms. The role of leverage deviations from the target on firms’ growth is analyzed by applying dynamic panel methodology of firms’ level annual accounting data. The results indicate that size of the firm, profitability, collateral values of assets, non-debt tax shield, firm-specific interest rate and spontaneous finance are significant determinants of the target leverage. It is found that firms, seldom have actual leverage equal to the target leverage, and more often the actual leverage deviate from the target level. This deviation, adversely affects the growth of firms. The empirical results indicate that upward deviation and downward deviation affect the company’s growth, differently. It is concluded that over-levered firms’ growth is more sensitive to leverage variance as compared to the under-levered firms

Economic case for stratified medicine

Thesis (S.M.)--Harvard-MIT Division of Health Sciences and Technology, 2007.Includes bibliographical references (leaves 36-39).The goal of this study is to explore the economic conditions that favor the joint development of therapeutics and companion diagnostics. I hypothesize that predictive biomarkers can generate economic value in drug development by increasing success rates. I construct an economic model of the development of a hypothetical new therapy, and devote particular attention to parameters regarding safety, efficacy, cost, and market size, within a decision-theoretic framework. The results include a characterization of the dynamic net present value trade-offs between stratum size and biomarker success, as well as the identification of two complementary concepts of stratified medicine, namely, disease reclassification and value-based reimbursement. I also identify a strong potential incentive mechanism in the hands of public policy makers that could facilitate a resolution of the tension between patient interests and the interests of pharmaceutical sponsors. The conclusion is that a biomarker can compensate for smaller stratum by increasing success probabilities. However, the effects of longer development time due to biomarker inclusion counter the effects of improved success probabilities. Longer exclusivity periods for stratified medicine may be required in order to resolve the tension between patient interests and the interests of pharmaceutical sponsors.by Amir Goren.S.M

Measurement of the vector and tensor analyzing powers for dp- elastic scattering at 880 MeV

The vector Ay and tensor analyzing powers Ayy and Axx for dp- elastic scattering were measured at Td = 880 MeV over the c.m. angular range from 60 to 140 degrees at the JINR Nuclotron. The data are compared with predictions of different theoretical models based on the use of nucleon-nucleon forces only. The observed discrepancies of the measured analyzing powers from the calculations require the consideration of additional mechanisms.Comment: 5 pages,3 figure

Do poor patients suffer from inaccurate diagnoses more than well-to-do patients? A randomized control trial

BACKGROUND: Poor patients have greater morbidity and die up to 10 years earlier than patients who have higher socio-economic status. These findings are often attributed to differences in life-style between groups. The present study aimed at investigating the extent to which physicians contribute to the effect by providing relative poorer care, resulting in relative neglect in terms of time spent with a poor patient and more inaccurate diagnoses. METHODS: A randomised experiment with 45 internal medicine residents. Doctors diagnosed 12 written clinical vignettes that were exactly the same except for the description of the patients' socio-economic status. Each participant diagnosed four of the vignettes in a poor-patient version, fou

Gauge Issues in Extended Gravity and f(R) Cosmology

We consider issues related to the conformal mapping between the Einstein and Jordan frames in f(R) cosmology. We consider the impact of the conformal transformation on the gauge of a perturbed system and show that unless the system is written in a restricted set of gauges the mapping could produce an inconsistent result in the target frame. Newtonian gauge lies within the restricted group but synchronous gauge does not. If this is not treated carefully it could in principle contaminate numerical calculations.Comment: 12 pages, REVTeX4. Replaced with version accepted by JCAP. Citations added and some clarification

Outcomes following Microvascular Mandibular Reconstruction in Pediatric Patients and Young Adults

Background: The etiology and treatment of complex mandibular defects in children differ markedly from those of adults, although treatment with free bone flaps is historical in both groups. While adult outcomes and complication rates are well known, few pediatric data exist, especially for patients with congenital deficiencies. This study reports early and late outcomes from a cohort of young, primarily syndromic patients undergoing microvascular mandibular reconstruction. Methods: This is a retrospective case series of patients who underwent microvascular mandibular reconstruction between 1995 and 2016. Results: Thirteen patients received a total of 13 fibula transfers and 1 medial femoral condyle transfer. Most patients carried a congenital diagnosis (77%), and the average age during surgery was 11.7 ± 5.7 years. The median (interquartile range) [IQR] length of follow-up was 6.3 (5.7) years. There was a 100% flap survival rate, although 86% of all patients experienced at least one complication. Half of all procedures resulted in an early complication. Nine patients (69%) developed late complications, of which temporal mandibular joint ankylosis was the most common (n = 5; 38%). Conclusions: This study is one of few detailing outcomes following mandibular reconstruction by free flap transfer in pediatric patients. These patients were primarily syndromic with appreciable complication rates higher than in other adult and pediatric studies. Some complications are manageable or self-resolving, but others lead to functional problems that may require late operative interventions to correct. Microsurgical treatment should be reserved for children with large, complex mandibular defects when other options are unavailable or have been exhausted

Personalized peptide-based vaccination for treatment of colorectal cancer: rational and progress

Colorectal cancer (CRC) is one of the most common cancers globally and is associated with a high rate of morbidity and mortality. A large proportion of patients with early stage CRC who undergo conventional treatments develop local recurrence or distant metastasis and in this group of advanced disease, the survival rate is low. Furthermore there is often a poor response and/or toxicity associated with chemotherapy and chemo-resistance may limit continuing conventional treatment alone. Choosing novel and targeted therapeutic approaches based on clinicopathological and molecular features of tumors in combination with conventional therapeutic approach could be used to eradicate residual micrometastasis and therefore improve patient prognosis and also be used preventively. Peptide-based vaccination therapy is one class of cancer treatment that could be used to induce tumor-specific immune responses, through the recognition of specific antigen-derived peptides in tumor cells, and this has emerged as a promising anti-cancer therapeutic strategy. The aim of this review was to summarize the main findings of recent studies in exciting field of peptide-based vaccination therapy in CRC patients as a novel therapeutic approach in treatment of CRC