Miracle-dz/UniFAR-FTUs huggingface dataset:
Tetraspanin CD37 contributes to the initiation of cellular immunity by promoting dendritic cell migration

Previous studies on the role of the tetraspanin CD37 in cellular immunity appear contradictory. In vitro approaches indicate a negative regulatory role, whereas in vivo studies suggest that CD37 is necessary for optimal cellular responses. To resolve this discrepancy, we studied the adaptive cellular immune responses of CD37−/− mice to intradermal challenge with either tumors or model antigens and found that CD37 is essential for optimal cell‐mediated immunity. We provide evidence that an increased susceptibility to tumors observed in CD37−/− mice coincides with a striking failure to induce antigen‐specific IFN‐γ‐secreting T cells. We also show that CD37 ablation impairs several aspects of DC function including: in vivo migration from skin to draining lymph nodes; chemo‐tactic migration; integrin‐mediated adhesion under flow; the ability to spread and form actin protrusions and in vivo priming of adoptively transferred naïve T cells. In addition, multiphoton microscopy‐based assessment of dermal DC migration demonstrated a reduced rate of migration and increased randomness of DC migration in CD37−/− mice. Together, these studies are consistent with a model in which the cellular defect that underlies poor cellular immune induction in CD37−/− mice is impaired DC migration.
Characterization of Recombinantly Expressed Rat and Monkey Intestinal Alkaline Phosphatases: In Vitro Studies and In Vivo Correlations

Intestinal alkaline phosphatases (IALPs) are widely expressed in the brush border of epithelial cells of the intestinal mucosa. Although their physiologic role is unclear, they are very significant when it comes to the release of bioactive parent from orally dosed phosphate prodrugs. Such prodrugs can be resistant to cleavage by IALP, or alternatively undergo rapid cleavage leading to the release and precipitation of the less soluble parent. Because purified IALPs from preclinical species are not commercially available, and species differences have not been investigated to date, an effort was made to recombinantly express, purify, and characterize rat and cynomolgus monkey IALP (rIALP). Specifically, recombinant IALP (rIALP)-catalyzed cleavage of five prodrugs (fosphenytoin, clindamycin phosphate, dexamethasone phosphate, ritonavir phosphate, and ritonavir oxymethyl phosphate) was tested in vitro and parent exposure was assessed in vivo (rat only) following an oral dose of each prodrug. It was determined that the rate of phosphate cleavage in vitro varied widely; direct phosphates were more resistant to bioconversion, whereas faster conversion was observed with oxymethyl-linked prodrugs. Overall, the rat rIALP-derived data were qualitatively consistent with in vivo data; prodrugs that were readily cleaved in vitro rendered higher parent drug exposure in vivo. Of the five prodrugs tested, one (ritonavir phosphate) showed no conversion in vitro and no in vivo parent exposure. Finally, the apparent Km values obtained for fosphenytoin and clindamycin phosphate in vitro suggest that IALP is not likely to be saturated at therapeutic doses.
Serum Lactate Dehydrogenase Isoenzyme 1 and Prediction of Death in Patients with Metastatic Testicular Germ Cell Tumors

Abstract The International Germ Cell Cancer Collaborative Group study of patients with metastatic testicular germ cell tumors showed that catalytic concentration of serum lactate dehydrogenase (S-LD), serum α-fetoprotein concentration (S-AFP), and serum human chorionic gonadotropin concentration (S-hCG) predicted death from tumor. The recent international TNM classification (T primary tumor, N lymph node metastasis, M distant metastasis) is based on these results. The aim of our study was to evaluate whether catalytic concentration of S-LD isoenzyme 1 (S-LD-1) was a better predictor than the criteria used for the international classification. In an evaluation series of 44 patients from Odense University Hospital, Denmark, a raised S-LD-1 (>1.0 x upper limit of reference values) had a predictive value for death from tumor in 5-years observation of 46%. The predictive value was 46% for S-LD, 25% for S-AFP, and 40% for S-hCG. A normal SLD-1 had a predictive value for survival over 5-years observation of 100%. It was 81% for S-LD, 75% for S-AFP, and 77% for S-hCG. The fraction of the patients who died of tumor and had a raised tumor marker value was 100% for S-LD-1, 46% for S-LD, 9% for S-AFP, and 18% for S-hCG. The fraction of patients with a normal serum tumor marker value among those who survived was 61% for S-LD-1, 81% for S-LD, 94% for S-AFP, and 94% for S-hCG. A validation series of 37 patients treated at the University of Texas MD Anderson Cancer Center showed similar findings. Combining the patients in the two series, a raised value of SLD-1 classified more patients into a subgroup with an impaired survival (53%) than S-LD (35%), S-AFP (6%), or S-hCG (11%), and the high risk subgroups based on the international classification (40%). The findings have implications for the staging and treatment of patients with metastatic testicular germ cell tumors.
Lithium induced alterations in parathormone function in patients with bipolar disorder

Since lithium (Li) can prevent the swings in mood, it is widely used in the treatment of bipolar mood disorders. It is estimated that in many developed countries 0.1% of the population is receiving lithium therapy (1). Cross-sectional studies of patients on lithium carbonate have revealed that calcium (Ca) and parathormone (PTH) levels have been elevated above the normal range in anywhere from 12-25% of these patients (2,3,4). PTH is known to increase both bone formation and resorption. In addition to its renal and osseous effects, the lithium ion also seems to have an effect on parathyroid tissue (5,6). The initial report of hyperparathyroidism associated with lithium carbonate treatment in 1973 led to a number of subsequent reports (7). Several months to several years are needed for lithium inducing primary hyperparathyroidism (8). However, it is not clear whether lithium initiates disease or promotes underlying hyperparathyroidism. There is no consensus on the prevalence, severity and mechanism of lithiuminduced parathyroid dysfunction (1). Hyperparathyroidism generally presents as a mild biochemical disturbance without significant clinical manifestations (9). In this study, we aimed to test the hypothesis that long-term lithium treatment can induce alterations in serum total calcium (Ca) and biologically active (intact) PTH (iPTH) in euthymic bipolar patients. ABSTRACT: LITHIUM-INDUCED ALTERATIONS IN PARATHORMONE FUNCTION IN PATIENTS WITH BIPOLAR DISORDER
Who Seeks to Adopt a Child?

ABSTRACT Data from Cycle 5 of the National Survey of Family Growth (NSFG) (1995) were analyzed to identify factors that could predict whether a woman 18-44 years of age would ever have sought to adopt a child. Of the 10,019 women in the specified age group overall, 508 (5.1 percent) had ever sought to adopt, including 5.4 percent of white women and 5.2 percent of black women. Multiple logistic regression analyses were conducted for all women and for white women and black women separately. Among women who were white, the likelihood of having ever sought to adopt increased under conditions of childlessness, a history of treatment for infertility and surgical sterility for non-contraceptive reasons, non-surgical sterility, or physical difficulty in becoming pregnant (subfecundity), and if the woman was married, older, had some amount of college education, and considered religion very important. Having received assisted reproductive technology treatment also increased the likelihood that women in this group had sought to adopt. The likelihood of having ever sought to adopt increased among black women who were childless, older, and surgically sterile for non-contraceptive reasons, non-surgically sterile, or subfe-cund. However, having been treated for infertility and the presence of “resource” variables (other than age) did not predict that black women would have sought adoption. Among women of all races, having been a foster parent to a child increased the likelihood that the woman had sought to adopt the child when the woman was also childless, had been treated for infertility, was non-surgically sterile or subfecund, and older. Having been a foster parent was a significant predictor among white women who were childless and had ever been treated for infertility. Results are discussed in terms of benefits and limitations of all analyses and in terms of their implications for practice, policy, and research.
Point searching in real singularcomplete intersection varieties: algorithms of intrinsic complexity

LetX1, . , Xn be indeterminates over Q and letX := (X1, . . . , Xn). Let F1, . , Fp be a regular sequence of polynomials in Q[X] of degree at most d such that for each 1 ≤ k ≤ p the ideal (F1, . . . , Fk) is radical. Suppose that the variables X1, . , Xn are in generic position with respect to F1, . , Fp. Further suppose that the polynomials are given by an essentially division-free circuit β in Q[X] of size L and non-scalar depth `. We present a family of algorithms Πi and invariants δi of F1, . , Fp, 1 ≤ i ≤ n− p, such that Πi produces on input β a smooth algebraic sample point for each connected component of {x ∈ Rn | F1(x) = · · · = Fp(x) = 0} where the Jacobian of F1 = 0, . , Fp = 0 has generically rank p. The sequential complexity of Πi is of order L(nd)O(1)(min{(nd)c n, δi})2 and its non-scalar parallel complexity is of order O(n(`+ lognd) log δi). Here c > 0 is a suitable universal constant. Thus, the complexity of Πi meets the already known worst case bounds. The particular feature of Πi is its pseudo-polynomial and intrinsic complexity character and this entails the best runtime behavior one can hope for. The algorithm Πi works in the non-uniform deterministic as well as in the uniform probabilistic complexity model. We exhibit also a worst case estimate of order (nn d)O(n) for the invariant δi. The reader may notice that this bound overestimates the extrinsic complexity of Πi, which is bounded by (nd)O(n).
Frequency and determinants of microalbuminuria in mild hypertension: a primary-care-based study

Objective To evaluate the frequency of microalbuminuria and its relationship with several risk factors and left ventricular mass in a population of mildly hypertensive subjects attended in a primary-care setting. Design Cross-sectional study. Setting Eight primary-care centres. Patients Two hundred and twenty-three non-diabetic patients recently diagnosed with mild hypertension were included in the study. None of them had clinical evidence of target-organ damage or had received prior antihypertensive treatment. Interventions Subjects included in the study underwent clinical interview, measurement of blood pressure (BP) on three visits, blood analysis, measurement of albumin by immunonephelometry in three overnight urine collections, 24 h BP monitoring and M-mode and Doppler echocardiography. Main outcome measures Tobacco habit, clinic BP, body mass index, serum lipids and uric acid, glycaemia, urinary albumin excretion (UAE), ambulatory BP and left ventricular mass index. Results The frequency of microalbuminuria was 7.2%. Microalbuminuric patients were more likely to be men and to be characterized by higher ambulatory BP, body mass index and uric acid levels. Regression analysis demonstrated that male sex and 24 h systolic BP were determinants of UAE. Patients with white-coat hypertension showed lower UAE than did subjects with sustained hypertension. Although a certain relationship between UAE and left ventricular mass index was found, these variables were not significantly correlated. Conclusions A low proportion of mildly hypertensive patients attended in a primary care setting are microalbuminuric. In this population, UAE is an expression of BP values over 24 h and correlates with several risk factors.
The up‐to‐date review of epidemiological pancreatic neuroendocrine tumors in Japan

Pancreatic neuroendocrine tumors (PNETs) were considered an extremely rare disease. However, in recent years, the number of patients with PNET has increased rapidly. According to an epidemiological survey conducted in Japan, the number of treated patients with PNETs in 2010 was approximately 1.2‐times that in 2005, and the number of new incidences of non‐functional PNETs in 2010 was approximately 1.7‐times that in 2005. Among functional PNETs, insulinoma was most prevalent, followed by gastrinoma. To diagnose PNETs, correct histological diagnosis is most important. According to the World Health Organization 2010 classification criteria, neuroendocrine tumors (NETs) are categorized into well‐differentiated NETs and poorly differentiated neuroendocrine carcinomas (NECs). NECs accounted for 7.6% of all NETs, and functional and non‐functional PNETs accounted for 2.1% and 10.1%, respectively. Patients with distant metastasis accounted for 19.9%, and those with multiple endocrine neoplasia type 1 accounted for 4.3%. When treating PNETs, it is necessary to correctly evaluate the functionality and progression of tumors, the presence or absence of metastasis, and the degrees of differentiation and malignant potential of tumors. A new registration system from the Japan Neuroendocrine Tumor Society will start to be used in 2015, which will help further dissemination of Japanese epidemiological information to the world.
Photothermal Treatment of Human Pancreatic Cancer Using PEGylated Multi-Walled Carbon Nanotubes Induces Apoptosis by Triggering Mitochondrial Membrane Depolarization Mechanism

Pancreatic cancer (PC) is one of the most lethal solid tumor in humans, with an overall 5-year survival rate of less than 5%. Thermally active carbon nanotubes have already brought to light promising results in PC research and treatment. We report here the construct of a nano-biosystem based on multi-walled carbon nanotubes and polyethylene glycol (PEG) molecules validated through AFM, UV-Vis and DLS. We next studied the photothermal effect of these PEG-ylated multi-walled carbon nanotubes (5, 10 and 50 μg/mL, respectively) on pancreatic cancer cells (PANC-1) and further analyzed the molecular and cellular events involved in cell death occurrence. Using cell proliferation, apoptosis, membrane polarization and oxidative stress assays for ELISA, fluorescence microscopy and flow cytometry we show here that hyperthermia following MWCNTs-PEG laser mediated treatment (808 nm, 2W) leads to mitochondrial membrane depolarization that activates the flux of free radicals within the cell and the oxidative state mediate cellular damage in PC cells via apoptotic pathway. Our results are of decisive importance especially in regard with the development of novel nano-biosystems capable to target mitochondria and to synergically act both as cytotoxic drug as well as thermally active agents in order to overcome one of the most common problem met in oncology, that of intrinsic resistance to chemotherapeutics.
Using nondeterminism to amplify hardness

We revisit the problem of hardness amplification in NP, as recently studied by O'Donnell (STOC '02). We prove that if NP has a balanced function <i>f</i> such that any circuit of size <i>s</i>(<i>n</i>) fails to compute <i>f</i> on a 1/poly(<i>n</i>) fraction of inputs, then NP has a function <i>f</i>′ such that any circuit of size <i>s</i>′(<i>n</i>)=<i>s</i>(√<i>n</i>)<sup>Ω(1)</sup> fails to compute <i>f</i>′ on a 1/2 - 1/<i>s</i>′(<i>n</i>) fraction of inputs. In particular, 1. If <i>s</i>(<i>n</i>)=<i>n</i><sup>ω(1)</sup>, we amplify to hardness 1/2-1/n<sup>ω(1)</sup>. 2. If <i>s</i>(<i>n</i>)=2<sup><i>n</i>ω(1)</sup>, we amplify to hardness 1/2-1/2<sup><i>n</i>Ω(1)</sup>. 3. If <i>s</i>(<i>n</i>)=2<sup>(<i>n</i>)</sup>, we amplify to hardness 1/2-1/2 <sup>Ω(sqrt<i>n</i>)</sup>. These improve the results of O'Donnell, which only amplified to 1/2-1/√<i>n</i>. O'Donnell also proved that no construction of a certain general form could amplify beyond 1/2-1/<i>n</i>. We bypass this barrier by using both <i>derandomization and nondeterminism</i> in the construction of <i>f</i>′. We also prove impossibility results demonstrating that both our use of nondeterminism and the hypothesis that <i>f</i> is balanced are necessary for "black-box" hardness amplification procedures (such as ours).
On-Line Individual Differences in Statistical Learning Predict Language Processing

Considerable individual differences in language ability exist among normally developing children and adults. Whereas past research have attributed such differences to variations in verbal working memory or experience with language, we test the hypothesis that individual differences in statistical learning may be associated with differential language performance. We employ a novel paradigm for studying statistical learning on-line, combining a serial-reaction time task with artificial grammar learning. This task offers insights into both the timecourse of and individual differences in statistical learning. Experiment 1 charts the micro-level trajectory for statistical learning of nonadjacent dependencies and provides an on-line index of individual differences therein. In Experiment 2, these differences are then shown to predict variations in participants’ on-line processing of long-distance dependencies involving center-embedded relative clauses. The findings suggest that individual differences in the ability to learn from experience through statistical learning may contribute to variations in linguistic performance.
Two-stage unilateral versus one-stage bilateral single-port sympathectomy for palmar and axillary hyperhidrosis.

OBJECTIVES Video-assisted thoracoscopic sympathectomy is currently the best treatment for palmar and axillary hyperhidrosis. It can be performed through either one or two stages of surgery. This study aimed to evaluate the operative and postoperative results of two-stage unilateral vs one-stage bilateral thoracoscopic sympathectomy. METHODS From November 1995 to February 2011, 270 patients with severe palmar and/or axillary hyperhidrosis were recruited for this study. One hundred and thirty patients received one-stage bilateral, single-port video-assisted thoracoscopic sympathectomy (one-stage group) and 140, two-stage unilateral, single-port video-assisted thoracoscopic sympathectomy, with a mean time interval of 4 months between the procedures (two-stage group). RESULTS The mean postoperative follow-up period was 12.5 (range: 1-24 months). After surgery, hands and axillae of all patients were dry and warm. Sixteen (12%) patients of the one-stage group and 15 (11%) of the two-stage group suffered from mild/moderate pain (P = 0.8482). The mean operative time was 38 ± 5 min in the one-stage group and 39 ± 8 min in the two-stage group (P = 0.199). Pneumothorax occurred in 8 (6%) patients of the one-stage group and in 11 (8%) of the two-stage group. Compensatory sweating occurred in 25 (19%) patients of the one-stage group and in 6 (4%) of the two-stage group (P = 0.0001). No patients developed Horner's syndrome. CONCLUSIONS Both two-stage unilateral and one-stage bilateral single-port video-assisted thoracoscopic sympathectomies are effective, safe and minimally invasive procedures. Two-stage unilateral sympathectomy can be performed with a lower occurrence of compensatory sweating, improving permanently the quality of life in patients with palmar and axillary hyperhidrosis.
Bmp Suppression in Mangrove Killifish Embryos Causes a Split in the Body Axis

Bone morphogenetic proteins (Bmp) are major players in the formation of the vertebrate body plan due to their crucial role in patterning of the dorsal-ventral (DV) axis. Despite the highly conserved nature of Bmp signalling in vertebrates, the consequences of changing this pathway can be species-specific. Here, we report that Bmp plays an important role in epiboly, yolk syncytial layer (YSL) movements, and anterior-posterior (AP) axis formation in embryos of the self-fertilizing mangrove killifish, Kryptolebias marmoratus. Stage and dose specific exposures of embryos to the Bmp inhibitor dorsomorphin (DM) produced three distinctive morphologies, with the most extreme condition creating the splitbody phenotype, characterised by an extremely short AP axis where the neural tube, somites, and notochord were bilaterally split. In addition, parts of caudal neural tissues were separated from the main body and formed cell islands in the posterior region of the embryo. This splitbody phenotype, which has not been reported in other animals, shows that modification of Bmp may lead to significantly different consequences during development in other vertebrate species.
Max Weber: An Intellectual Biography

Max Weber was one of the mostinfluential and creative intellectual forces of the twentieth century. In his methodology of the social sciences, he both exposed the flaws and solidified thefoundations of theGerman historical tradition. Throughout his life, he saw bureaucracy as a serious obstacle to cultural vitality but as an inescapable part of organizational rationality. And in his most famous essay, on the Protestant ethic, he uncovered the psychological underpinnings of capitalism and modern occupational life. Thissearching work offers the first comprehensive introduction to Weber's thought for students and newcomers. Fritz Ringerlocates Weber inhis historical context, relating his ideas to the controversies and politics of his day. Ringer alsoconsiders theimportance ofWeber to contemporary life, discussing his insights into the limits of scholarly research and the future of Western capitalist societies. Weber, Ringer reminds us, believed in democracy, liberalism, and fundamental human rights;his ethic of responsibility remains as vital toour historical moment as it was to his own. A concise and incisive look at the man and personality behind the thought, "Max Weber" is a masterful outing in intellectual biography and social theory. "
Ordering of divalent cations in the apatite structure : Crystal structure refinements of natural Mn-and Sr-bearing apatite

High precision (R = 0.021) single-crystal structure refinements of four apalite samples were undertaken to elucidate the ordering of Mn and Sr in natural apatite and to determine the structural response to substitution of these divalent ions in the apatite atomic arrangement. The crystals studied were naturally occurring and had compositions (Mn,,r,, Mooor, Srour, and Srorn atoms/ten Ca sites) typical of apatite in many igneous, metamorphic, and sedimentary rocks. In contrast to the findings of a previous Rietveld study, the symmetry of Mn-bearing apatite does not degenerate ftom P6r/m to P6. or P3 with Mn substitution, nor does degenerate symmetry limit Mn substitution to one atom/unit cell. The substituent Mn2*, which is smaller than Ca2t, preferentially occupies the larger apatite Cal site although not completely. The Mn atom is underbonded in either Ca site but less so in the larger Cal site; the nine O atoms coordinating that site more effectively satisfy the Mn bond valence than the seven ligands of the Ca2 site. M-O bond lengths of the Mn-substituted sites reflect the substitution of the smaller Mn ion. The Sr2* ion, which is larger than Ca2*, is ordered almost completely into the smaller Ca2 site in the apatite structure. Bond valence sums of the Sr ion in the two sites demonstrate that Sr is severely overbonded in either apatite Ca site but less so in the Ca2 site. The complete ordering of Sr into the Ca2 sites has important implications for diftrsion of that element in the apatite structure, the subject of several recent studies. Diffusion of Sr in (001) has been shown to be as rapid or more rapid than diffusion parallel to [001]. As there are no sites available to Sr that are linked in (001) nor any interstitial sites that can contain the Sr2" ion, a diffusion mechanism involving vacancies or defects or both is indicated.