Miracle-dz/UniFAR-FTUs huggingface dataset:
On the mechanism of intestinal absorption of drugs.

The intestinal absorption of acidic drugs is decreased severalfold and the absorption of basic drugs increased severalfold when the pH of the intestinal contents is raised from 4 to 8. This supports the hypothesis that the intestinal mucosa preferentially allows the absorption of the unionized form of a drug. Significant steady state concentration gradients of drugs are maintained between the gut lumen and plasma. Bases are concentrated within the gut lumen and acids are concentrated in plasma. These concentration ratios can be attributed to a slightly acidic environment at the intestinalblood barrier. There is a sufficient association between absorption of drugs and the lipid: water partition coefficients of their unionized moieties to justify the continued assumption that the gastrointestinal cell membranes are essentially lipoidal. Highly lipid-soluble drugs are in general rapidly absorbed while decidedly lipid-insoluble drugs are in general poorly absorbed.
Stiffness Modulation of A 1-DOF Robotic Manipulator with Antagonistic Actuators

-Stiffness modulation scheme for a robotic driving system with redundant actuation was investigated in this paper. The dynamic and the stiffness models of a simple system having one link and two prismatic actuators were derived and employed for computational simulations of dynamic response to an initial disturbance. Several combinations with different types of elastic elements were applied to the system and their movement were analysed. Keywords-stiffness modulation; redundant actuation; antagonistic stiffness; musculoskeletal structure
Putnam’s indispensability argument revisited, reassessed, revived

Crucial to Hilary Putnam’s realism in the philosophy of mathematics is to maintain the objectivity of mathematics without the commitment to the existence of mathematical objects. Putnam’s indispensability argument was devised as part of this conception. In this paper, I reconstruct and reassess Putnam’s argument for the indispensability of mathematics, and distinguish it from the more familiar, Quinean version of the argument. Although I argue that Putnam’s approach ultimately fails, I develop an alternative way of implementing his form of realism about mathematics that, by using different resources than those Putnam invokes, avoids the difficulties faced by his view.
Influence of Diabetes on the Myocardium and Coronary Arteries of Rhesus Monkey Fed an Athero genie Diet

To examine the influence of diabetes on the progression of coronary atherosclerosis and primary myocardial alterations in the rhesus monkey, a Purina or atherogenic diet was fed to nondiabetic animals of groups 1 and 2, respectively, and also to groups 3 and 4 with alloxan diabetes. After 18 months, cardiac studies were performed, by indicator dilution in the intact anesthetized state, at similar levels of heart rate and aortic pressure. Despite comparable basal hemodynamics, preload increments with saline evoked a stroke work response that was significantly less in both diabetic groups. Left ventricular end-diastolic pressure rose from 10.1 ± 1.4 mm Hg to 20.5 ± 2.7 in group 3, and from 11.1 ± 2.1 to 24.0 ± 3.3 in group 4, which were significantly higher elevations than occurred in the controls. End-diastolic volume rose much less in diabetics. Indices of contractility as well as left heart weight were normal Hydroxyproline concentrations were 4.98 ± 0.33 g/mg dry weight in group 1, 5.16 ± 0.24 in group 2, 8.4 ± 0.35 in group 3, and 7.1 ± 0.37 in group 4. Soluble collagen was significantly diminished and the insoluble fraction enhanced in diabetics and was the apparent basis for enhanced wall stiffness. The collagen increment was most evident between myoflbers. Cardiac cell organellee by electron microscopy, tissue cation concentrations, as well as the myocardial lactate response to pacing, were within normal limits. Cholesterol content of the coronary arteries, as a measure of the early atherosclerotic process observed as lipid streaks, was similarly increased in the nondiabetic and diabetic monkeys on lipid diets, with respective plasma cholesterols of 367 ± 55 and 408 ± 62 mg/100 ml. The diabetic-Purina group had a lower but significantly elevated coronary artery cholesterol, associated with higher plasma glucose and nonsterol lipid levels. Thus, in this primate model, diabetes did not intensify either the early coronary lesions induced by moderate hypercholesterolemia, nor were the myocardial changes associated with diabetes altered by the presence of moderate hypercholesterolemia.
Targeted Infection of Endothelial Cells by Avian Influenza Virus A/FPV/Rostock/34 (H7N1) in Chicken Embryos

ABSTRACT The tissue tropism and spread of infection of the highly pathogenic avian influenza virus A/FPV/Rostock/34 (H7N1) (FPV) were analyzed in 11-day-old chicken embryos. As shown by in situ hybridization, the virus caused generalized infection that was strictly confined to endothelial cells in all organs. Studies with reassortants of FPV and the apathogenic avian strain A/chick/Germany/N/49 (H10N7) revealed that endotheliotropism was linked to FPV hemagglutinin (HA). To further analyze the factors determining endotheliotropism, the HA-activating protease furin was cloned from chicken tissue. Ubiquitous expression of furin and other proprotein convertases in the chick embryo indicated that proteolytic activation of HA was not responsible for restriction of infection to the endothelium. To determine the expression of virus receptors in embryonic tissues, histochemical analysis of α2,3- and α2,6-linked neuraminic acid was carried out by lectin-binding assays. These receptors were found on endothelial cells and on several epithelial cells, but not on tissues surrounding endothelia. Finally, we analyzed the polarity of virus maturation in endothelial cells. Studies on cultured human endothelial cells employing confocal laser scanning microscopy revealed that HA is specifically targeted to the apical surface of these cells, and electron microscopy of embryonic tissues showed that virus maturation occurs also at the luminar side. Taken together, these observations indicate that endotheliotropism of FPV in the chicken embryo is determined, on one hand, by the high cleavability of HA, which mediates virus entry into the vascular system, and, on the other hand, by restricted receptor expression and polar budding, which prevent spread of infection into tissues surrounding endothelia.
In search of plentiful universal donor plasma: what might Landsteiner say?

Since the US military experience with aggressive plasma transfusion heralded a new ratio-driven massive transfusion protocol (MTP), subsequently endorsed by an evidence-based review, many transfusion services in the United States have adopted up-front plasma transfusion as part of an institutional MTP. Thawed plasma is widely used for this purpose, and group AB plasma is in great demand since blood component resuscitation in severely injured patients precedes ABO group determination. Simultaneously, blood centers have adopted strategies to reduce the risk of transfusion-related acute lung injury (TRALI), often by deferring multiparous women from donating plasma for transfusion. This effort has been successful in TRALI mitigation. However, since group AB plasma is in great demand, such mitigation strategies typically exclude group AB donors. A recent study shows that residual TRALI cases disproportionately implicate AB plasma. A prospective randomized trial studying different plasma:platelet (PLT):red blood cell ratios in MTP is under way. Until the results of this trial are available, the demand for universal donor plasma will continue. In this context, it has been proposed that group A plasma may be seen as “universal plasma” in MTP protocols. In one trauma center with extensive helicopter transport to rural areas, group A plasma has been transfused as the emergencyrelease “universal” plasma since 2008 during air transport using predefined criteria. Another group found that twothirds of 100 group A blood donors screened had an anti-B titer less than 64 and proposed that such “low-titer” group A plasma may be explored as universal plasma. A recent review in TRANSFUSION advocates for lowtiter group O whole blood in the military environment and eloquently summarizes the risk of hemolysis from the transfusion of blood components containing ABOincompatible plasma in the context of PLT transfusion. While most such hemolytic reactions have occurred when group O PLTs are transfused to group A patients, severe reactions have been reported when PLTs from a group A donor with a particularly high anti-B titer were transfused to two different patients. In addition, the prevalence of group B patients may be higher than 11% in large urban Level I trauma centers in the United States serving a high proportion of nonwhite populations. Another approach to providing plasma up-front for trauma resuscitation is the possibility of rapidly determining a patient’s ABO group at the bedside, an area that does not appear to have been emphasized. Bedside ABO agglutination tests as the final blood administration safety check have been used in some jurisdictions, notably France. A point-of-care method for Rh(D) typing was evaluated in the United States, although not ultimately approved. Perhaps the development of a bedside ABO point-of-care test in the civilian prehospital setting— where other point-of-care tests are already being used— would complement the options available to blood centers and transfusion services contemplating the imbalance between the supply and demand of group AB plasma.
Saccharomyces cerevisiae cdc15 mutants arrested at a late stage in anaphase are rescued by Xenopus cDNAs encoding N-ras or a protein with beta-transducin repeats

We have constructed a Xenopus oocyte cDNA library in a Saccharomyces cerevisiae expression vector and used this library to isolate genes that can function in yeast cells to suppress the temperature sensitive [corrected] defect of the cdc15 mutation. Two maternally expressed Xenopus cDNAs which fulfill these conditions have been isolated. One of these clones encodes Xenopus N-ras. In contrast to the yeast RAS genes, Xenopus N-ras rescues the cdc15 mutation. Moreover, overexpression of Xenopus N-ras in S. cerevisiae does not activate the RAS-cyclic AMP (cAMP) pathway; rather, it results in decreased levels of intracellular cAMP in both mutant cdc15 and wild-type cells. Furthermore, we show that lowering cAMP levels is sufficient to allow cells with a nonfunctional Cdc15 protein to complete the mitotic cycle. These results suggest that a key step of the cell cycle is dependent upon a phosphorylation event catalyzed by cAMP-dependent protein kinase. The second clone, beta TrCP (beta-transducin repeat-containing protein), encodes a protein of 518 amino acids that shows significant homology to the beta subunits of G proteins in its C-terminal half. In this region, beta Trcp is composed of seven beta-transducin repeats. beta TrCP is not a functional homolog of S. cerevisiae CDC20, a cell cycle gene that also contains beta-transducin repeats and suppresses the cdc15 mutation.
[White-coat hypertension and risk factors in recently diagnosed hypertensive patients].

OBJECTIVE To determine the frequency of white-coat hypertension (WCH) and associated risk factors in recently diagnosed hypertensive patients. MATERIAL AND METHODS A cross-sectional study was carried out from January 1997 to December 1998. The reference population consisted of 195 patients presenting with systemic arterial hypertension (SAH) of less than 1-month evolution and receiving no medical treatment. According to Joint National Committee (JNCVI) criteria, 100 individuals with Stages I, II, and III SAH underwent the following procedures: clinical history; physical examination; electrocardiogram, serum creatinine; urianalysis, and ambulatory monitoring of arterial pressure (AMAP). RESULTS A total of 54% of patients were WCH carriers and 46% presented sustained hypertension (SH); 37% of WCH patients and 63% of SH patients had a family history of SAH, while 19.7% of WCH patients and 39.2% of SH patients presented with stage 1 retinopathy. Left ventricular hypertrophy was absent in all WCH patients and present in 21.7% of SH patients. A total of 31% of WCH patients and 50% of SH patients presented electrocardiographic changes. CONCLUSIONS A total of 54% of patients presented WCH. Clinical/epidemiologic profiles of WCH carriers and SH patients are different.
Carcinoembryonic antigen half-life is an early predictor of therapeutic effects in induction chemotherapy for liver metastases from colorectal cancer.

AIM We evaluated the relationship between carcinoembryonic antigen half-life (CEA-HL) in the early period of induction chemotherapy for patients with liver metastases from colorectal cancer (CRLM) and their clinicopathological response. PATIENTS AND METHODS Seventy-four patients with initially unresectable CRLM received FOLFOX with or without bevacizumab and 30 patients underwent hepatic resection. The CEA-HL in the early postoperative period was investigated, and the pathological response was classified according to tumor regression grade (TRG). RESULTS The CEA-HL after the third chemotherapeutic course (CEA-HL3) was significantly shorter in responders compared to non-responders. In the 30 patients who underwent hepatectomy, the CEA-HL3 was significantly shorter in the major or complete-pathological-response group for the TRGs than in the the partial-pathological-response group. If the patients were divided into two groups according to the median value of 20 days, progression-free survival and overall survival were significantly better in those with CEA-HL3 below the cut-off. CONCLUSION The CEA-HL is an early predictor of the pathological response and prognosis after induction chemotherapy for CRLM.
Optimal channel allocation for sensing-based cognitive radio systems in multichannel multiuser environment

This paper deals with the problem of allocating the multiple primary channels to the multiple secondary users in a sensing-based cognitive radio system. Traffic pattern deviation and SNR variation of the primary channels to each secondary user are exploited for the channel allocation. The sum-throughput of the secondary users is maximized by properly allocating the primary channels to the secondary users in a way of one-to-one mapping. The channel allocation can be realized via the sum-throughput maximization with interference constraint to the primary users. Numerical results show the throughput enhancement of the proposed channel allocation over the conventional one.
Visceral Leishmaniasis in the BALB/c Mouse: A Comparison of the Efficacy of a Nonionic Surfactant Formulation of Sodium Stibogluconate with Those of Three Proprietary Formulations of Amphotericin B

ABSTRACT In this study, treatment efficacies of a nonionic surfactant vesicle formulation of sodium stibogluconate (SSG-NIV) and of several formulations of amphotericin B were compared in a murine model of visceral leishmaniasis. Treatment with multiple doses of AmBisome, Abelcet, and Amphocil (total dose, 12.5 mg of amphotericin B/kg of body weight) resulted in a significant suppression of parasite burdens in liver (P < 0.0005) and spleen (P < 0.0005) compared with those of controls, with Abelcet having the lowest activity. Only AmBisome and Amphocil gave significant suppression of parasites in bone marrow (compared to control values,P < 0.005). In the acute-infection model, single-dose treatments of SSG-NIV (296 mg of SbV/kg), SSG solution (296 mg of SbV/kg), or AmBisome (8 mg of amphotericin B/kg) were equally effective against liver parasites (compared to control values,P < 0.0005). SSG-NIV and AmBisome treatment also significantly suppressed parasites in bone marrow and spleen (P < 0.005), with SSG-NIV treatment being more suppressive (>98% suppression in all three sites). Free-SSG treatment failed to suppress spleen or bone marrow parasites. Infection status influenced treatment outcome. In the chronic-infection model, the AmBisome single-dose treatment was less effective in all three infection sites and the SSG-NIV single-dose treatment was less effective in the spleen. The results of this study suggest that the antileishmanial efficacy of SSG-NIV compares favorably with those of the novel amphotericin B formulations.
The fork head product directly specifies the tissue‐specific hormone responsiveness of the Drosophila Sgs‐4 gene.

Here we describe the identification of four binding sites of secretion enhancer binding protein 2 (SEBP2) in the regulatory region of the Drosophila salivary gland secretion protein gene 4 (Sgs‐4) and show that despite these sites' correspondence with previously described Broad‐Complex protein binding sites, SEBP2 is a Broad‐Complex‐independent factor encoded by the region‐specific homeotic gene fork head (fkh). Two of the Fork head/SEBP2 binding sites are located within an ecdysone response unit which controls the tissue‐ and stage‐specific responses of Sgs‐4 to the steroid hormone 20‐hydroxyecdysone. We demonstrate that these binding sites are relevant to the transcriptional activation of Sgs‐4 and show that Fork head also binds to the Sgs‐4 ecdysone response unit in vivo. Aside from being involved in the control of decisions during embryonic development, fkh thus participates directly in the control of specialized functions of differentiated cells at later stages of development.
ARN-509 in men with high-risk nonmetastatic castration-resistant prostate cancer (CRPC).

7 Background: ARN-509 is a novel second-generation anti-androgen that binds directly to the ligand-binding domain of the androgen receptor, impairing nuclear translocation and DNA binding. The Phase II portion of a multicenter Phase I/II study is evaluating the activity of ARN-509 in 3 distinct patient populations of men with CRPC (high risk non-metastatic CRPC, metastatic treatment-naïve CRPC, and progressive disease after abiraterone acetate). Preliminary results for the cohort of patients with high-risk non-metastatic CRPC are presented here. METHODS All patients had CRPC, no radiographic evidence of metastases (pelvic lymph nodes <3 cm below the iliac bifurcation were allowed), and high risk for disease progression based on PSA value ≥ 8 ng/mL within 3 months of enrollment and/or PSA doubling time ≤ 10 months. Patients received ARN-509 at the recommended Phase II dose of 240 mg/day, previously established in Phase I (Rathkopf et al, GU ASCO 2012). The primary endpoint was PSA response rate at 12 weeks according to the Prostate Cancer Working Group 2 Criteria. Secondary endpoints included safety, time to PSA progression and 1-year metastasis-free survival. PSA assessments were collected every 4 weeks and tumor scans were performed every 16 weeks. RESULTS Forty-seven patients were enrolled between November 2011 and May 2012. The median age was 71 years (range 51 to 88) and at baseline, patients presented with ECOG performance status 0 (77%), Gleason Score 8-10 (32%), and median PSA of 10.7 ng/mL. All patients received prior treatment with a LHRH analog with or without a first-generation anti-androgen. At a median treatment duration of 20 weeks, three patients discontinued the study. The most common treatment-related adverse events (AE) were fatigue (30%), diarrhea (28%), nausea (17%), rash (13%), and abdominal pain (11%). The incidence of Grade 3 AEs was 6.4%, and no seizures have been observed to date. The 12-week PSA response was 91% and the time to PSA progression has not been reached. CONCLUSIONS In men with high-risk non-metastatic CRPC, ARN-509 is safe and well tolerated with promising preliminary activity based on high PSA response rates. CLINICAL TRIAL INFORMATION NCT01171898.
The pituitary-gonadal axis in experimental nephrotic syndrome in male rats.

Basal and luteinizing releasing hormone-stimulated gonadotropin secretion were studied in male rats made nephrotic with puromycin, and in pair-fed and normal control animals. In addition, plasma concentrations of testosterone, androstenedione, estradiol, and estrone were measured in the three groups of animals. Urinary testosterone concentrations were also measured in the three experimental groups. The data showed that basal luteinizing hormone concentration was significantly elevated in the nephrotic group compared with the pair-fed and normal control groups. Gonadotropin response to luteinizing releasing hormone stimulation was not significantly different in the three groups, suggesting an intact hypothalamic-pituitary axis in nephrotic syndrome. Urinary testosterone concentration in the nephrotic animals was significantly higher than in the pair-fed and normal control groups. Plasma testosterone, androstenedione, estradiol, and estrone concentrations were significantly lower in the nephrotic and pair-fed animals than in the normal control animals, indicating possibly impaired gonadal steroidogenesis in these two groups that may be related to the catabolic state of the animals. It thus appears that urinary loss of protein-bound (sex hormone binding globulin-bound) testosterone in the nephrotic syndrome leads to increased basal secretion of luteinizing hormone, presumably as a result of increased luteinizing releasing hormone secretion. This occurs to compensate for the abnormal urinary testosterone loss and is an attempt to restore plasma testosterone concentrations to normal. The higher basal plasma luteinizing hormone concentration in the nephrotic group supports this conclusion. (ABSTRACT TRUNCATED AT 250 WORDS)
Propagation delay in RLC interconnection networks

The definition of Elmore's delay is extended to include inductance effects. The pulse delay of nonmonotonic rising node voltage in a tree-structured interconnection can be described by this new definition. The double moment matching method is presented. Based upon this approach, a closed-form formula for computing the second order moment of any tree-structured interconnection is established. The approach enables the derivation of computationally simple and closed-form formulas of signal propagation delays of nonmonotonic rising node voltages in tree-structured interconnections. The authors' results provide a new method for computing interconnection delay and reveal a critical link between net responses and net electrical properties. This formula set provides a tool to solve problems in the study of performance-driven-layout algorithms. <<ETX>>
NIH's Big Data to Knowledge initiative and the advancement of biomedical informatics

Two influential reports on data and computation from advisory committees to the NIH leadership resulted in important initiatives: (1) the report from the Working Group on Biomedical Computing for the Advisory Committee to the Director (ACD) of the National Institutes of Health (NIH) in 1999i led to the Biomedical Information Science and Technology Initiative (BISTI), and (2) the more recent report from the Working Group on Data and Informatics for the ACD in 2012ii led to the Big Data to Knowledge (BD2K) initiative.iii Several AMIA members participated in this working group. Both reports recommended strong support for data science and computation in biomedical sciences and healthcare. The BD2K initiative was launched at NIH in 2013 through the development of several focused workshops, calls for proposals for centers of excellence, for a data discovery index, for training programs, and through the creation of the new position of Associate Director of Data Sciences, reporting directly to the NIH director. According to Francis Collins, the charge is to “lead an NIH-wide priority initiative to take better advantage of the exponential growth of biomedical …