gebhart/patrepeval huggingface dataset:
About mean diameter and size distributions of poly(lactide-co-glycolide) (PLG) microspheres (2006)

Despite the importance of microsphere size for controlled drug delivery, little work has been done to quantitatively predict the distribution of microspheres from manufacturing techniques. This work presents a quantitative study that describes the size distribution of poly(lactide-co-glycolide) (PLG) microspheres. A fluid mechanics based correlation for the mean microsphere diameter is formulated based on the theory of emulsification in turbulent flow under non-coalescing conditions. The correlation was constructed and validated with experimentally obtained mean microsphere diameters prepared at different stirring speeds. In addition, a Rosin Rammler distribution function was found to give an accurate representation of the microsphere distribution. The spread of the microsphere size distribution was found to decrease with stirring speed. With the validation of the mathematical correlation, it is now possible to have a good estimate of the average microsphere size prior to microsphere preparation. This is directly relevant to the pharmaceutical industry where microspheres of specified mean diameter and size distribution are desirable.
Body Weight and Risk of Oral Contraceptive Failure (2002)

In Brief OBJECTIVE To examine the hypothesis that higher body weight increases the risk of oral contraceptive (OC) failure. METHODS We conducted a retrospective cohort analysis of data from 755 randomly selected female enrollees of Group Health Cooperative of Puget Sound who completed an in-person interview and dietary questionnaire between 1990 and 1994 as control subjects for a case-control study of ovarian cysts. Among the 618 women who were OC ever-users, we used Cox proportional hazards regression models to estimate the relative risk (RR) of pregnancy while using OCs associated with body weight quartile. RESULTS During 2822 person-years of OC use, 106 confirmed pregnancies occurred (3.8 per 100 person-years of exposure). After controlling for parity, women in the highest body weight quartile (70.5 kg or more) had a significantly increased risk of OC failure (RR 1.6, 95% confidence interval [CI] 1.1, 2.4) compared with women of lower weight. Higher elevations of risk associated with the highest weight quartile were seen among very low-dose OC users (RR 4.5, 95% CI 1.4, 14.4) and low-dose OC users (RR 2.6, 95% CI 1.2, 5.9), controlling for parity, race, religion, and menstrual cycle regularity. CONCLUSION Our findings suggest that body habitus may affect metabolism sufficiently to compromise contraceptive effectiveness. Consideration of a woman's weight may be an important element of OC prescription. The risk of becoming pregnant while using oral contraceptives is 60% higher for women weighing 70.5 kg or more than for women of lower weight.
Significantly Longer Progression-Free Survival With nab-Paclitaxel Compared With Docetaxel As First-Line Therapy for Metastatic Breast Cancer (2009)

This randomized study in first-line MBC demonstrated superior efficacy and safety of weekly nab-paclitaxel compared with docetaxel, with a statistically and clinically significant prolongation of PFS (> 5 months) in patients receiving nab-paclitaxel 150 mg/m(2) weekly compared with docetaxel 100 mg/m(2) q3w.
Hemostatic Factors and Replacement of Major Blood Loss with Plasma-Poor Red Cell Concentrates (1995)

The purpose of this study was to assess the change of platelet and fibrinogen concentrations and the change of activities of prothrombin and factors V and VII when major surgical blood loss was replaced with plasma-poor red cell concentrates (RCCs) and colloid plasma substitutes. Sixty patients were studied. The average blood loss was 65% +/- 41% of the calculated blood volume (CBV). Blood loss was monitored carefully and replaced without delay to ensure stable blood volume. Blood samples were obtained at the induction of anesthesia and at the end of the recovery room period, or before the patient was given fresh frozen plasma. In addition, a platelet count was determined after each 20% blood loss. The results were converted to relative values, and simple linear regression with logarithmic transformation was applied. The initial platelet concentration was 257 +/- 89 x 10(3)/mm3 and the extrapolation of the regression line intercepted the critical level of 50 x 10(3)/mm3 at 230% (confidence interval 169%-294%) blood loss. The initial fibrinogen concentration was 3.7 +/- 1.1 g/L and the hemostatically significant level of 1.0 g/L was already reached at 142% (117%-169%) blood loss (r2 = 0.90). Activities of prothrombin and coagulation factors V and VII reached their critical levels at 201% (160%-244%), 229% (167%-300%), and 236% (198%-277%) blood loss, respectively. We conclude that deficiency of fibrinogen develops earlier than any other hemostatic abnormality when plasma-poor RCCs are used for the replacement of major blood loss.
Survey of Nonlinear Attitude Estimation Methods (2006)

This paper provides a survey of modern nonlinear filtering methods for attitude estimation. Early applications relied mostly on the extended Kalman filter for attitude estimation. Since these applications, several new approaches have been developed that have proven to be superior to the extended Kalman filter. Several of these approaches maintain the basic structure of the extended Kalman filter, but employ various modifications in order to provide better convergence or improve other performance characteristics. Examples of such approaches include: filter QUEST, extended QUEST and the backwards-smoothing extended Kalman filter. Filters that propagate and update a discrete set of sigma points rather than using linearized equations for the mean and covariance are also reviewed. A twostep approach is discussed with a first-step state that linearizes the measurement model and an iterative second step to recover the desired attitude states. These approaches are all based on the Gaussian assumption that the probability density function is adequately specified by its mean and covariance. Other approaches that do not require this assumption are reviewed, Associate Professor, Department of Mechanical & Aerospace Engineering. Email: johnc@eng.buffalo.edu. Associate Fellow AIAA. Aerospace Engineer, Guidance, Navigation and Control Systems Engineering Branch. Email: Landis.Markley@nasa.gov. Fellow AIAA. Postdoctoral Research Fellow, Department of Mechanical & Aerospace Engineering. Email: cheng3@eng.buffalo.edu. Member AIAA.
Pomalidomide in combination with dexamethasone results in synergistic anti‐tumour responses in pre‐clinical models of lenalidomide‐resistant multiple myeloma (2016)

Pomalidomide is an IMiD(®) immunomodulatory agent, which has shown clinically significant benefits in relapsed and/or refractory multiple myeloma (rrMM) patients when combined with dexamethasone, regardless of refractory status to lenalidomide or bortezomib. (Schey et al, ; San Miguel et al, 2013; Richardson et al, 2014; Scott, ) In this work, we present preclinical data showing that the combination of pomalidomide with dexamethasone (PomDex) demonstrates potent anti-proliferative and pro-apoptotic activity in both lenalidomide-sensitive and lenalidomide-resistant MM cell lines. PomDex also synergistically inhibited tumour growth compared with single-agent treatment in xenografts of lenalidomide-resistant H929 R10-1 cells. Typical hallmarks of IMiD compound activity, including IKZF3 (Aiolos) degradation, and the downregulation of interferon regulatory factor (IRF) 4 and MYC, seen in lenalidomide-sensitive H929 MM cell lines, were also observed in PomDex-treated lenalidomide-resistant H929 MM cells. Remarkably, this resulted in strong, synergistic effects on the induction of apoptosis in both lenalidomide-sensitive and resistant MM cells. Furthermore, gene expression profiling revealed a unique differential gene expression pattern in PomDex-treated samples, highlighted by the modulation of pro-apoptotic pathways in lenalidomide-resistant cells. These results provide key insights into molecular mechanisms of PomDex in the lenalidomide-resistant setting.
A42867, a novel glycopeptide antibiotic. (1989)

A42867 is a new glycopeptide antibiotic of the ristocetin-vancomycin class active against aerobic and anaerobic Gram-positive bacteria. A42867 is produced by a strain of Nocardia nov. sp. ATCC 53492. A42867 was isolated during a screening program aimed at the discovery of new members of this glycopeptide class of antibiotics, by affinity chromatography based on an acyl-D-alanyl-D-alanine probe. The structure of A42867 was elucidated by fast atom bombardment MS, high field 2D 1H NMR spectroscopy, and HPLC analysis of the hydrolyzed carbohydrates. A42867 differs from vancomycin in the sugar portion and in the presence of only one chlorine atom in the peptide core. Its biological activity on Gram-positive aerobic and anaerobic bacteria is similar to that of other antibiotics of this group.
Transient transformation of Arabidopsis leaf protoplasts: a versatile experimental system to study gene expression (1994)

An improved protocol is reported to isolate and transiently transform mesophyll protoplasts of Arabidopsis thaliana. Transfected leaf protoplasts support high levels of expression of the bacterial reporter gene coding for beta-glucuronidase (GUS), under the control of the cauliflower mosaic virus (CaMV) 35S promoter. Transient expression of GUS activity was monitored spectrophotometrically and reached a maximum between 18 and 48 h after polyethylene glycol (PEG)-mediated DNA uptake. Histochemical staining for GUS activity revealed reproducible transformation frequencies between 40 and 60%, based on the number of protoplasts survived. To demonstrate the applicability of the transient expression system, the subcellular localization of GUS proteins tagged with different nuclear polypeptides was studied in transfected mesophyll protoplasts, revealing nuclear compartmentalization of the chimeric GUS enzymes. Furthermore, Arabidopsis mesophyll protoplasts support auxin-mediated induction of chloramphenicol acetyl-transferase (CAT) activity when transfected with a transcriptional fusion between the CAT reporter gene and the early auxin-inducible PS-IAA4/5 promoter. Hence, the method allows in vivo analysis of promoter activity and subcellular localization of fusion proteins in a homologous transformation system.
Collagen VI: A New Candidate Breast Cancer Marker Linked to Resistance to Platinum-Based Cancer Drugs (2012)

Abstract : We have observed a dramatic increase of adipocyte-derived matrix protein collagen VI (COL6) level during cancer progression, particularly it relates to a discrete C-terminal domain of the alpha3 subunit of COL6. I have established 2 lines of transgenic mice which overproduce C-terminal domain, called C5, of the COL6A3 (COL6A3-C5) under the control of MMTV promoter and crossed with MMTV-PyMT mice to see the C5 effects on mammary tumor progression in vivo. Our results indicate that COL6A3-C5 augments primary tumor growth and pulmonary metastasis in MMTV-PyMT mammary tumor mice model in vivo. Based on the cDNA microarray data with tumor tissues, COL6A3-C5 seems to be a signaling molecule regulating a kinase (or a phosphatase) activity which may be through a specific receptors that remains to be identified. Furthermore, treatment with COL6A3-C5 neutralizing antibodies in MMTV-PyMT mice protects mammary tumor progression. I have determined the effects of COL6 on the TZD mediated enhancement of cisplatin susceptibility with PyMT/COL6-/- mice. Tumor growth in PyMT/COL6-/- mice was significantly attenuated either by cisplatin or by a combination of cisplatin and TZD compared to PyMT/COL6+/+. To better understand the COL6 effects on drug resistance, I have tested COL6A3-C5 neutralizing antibodies in combination with cisplatin and TZD using the primary cultured tumor cells implantation system. To visualize the tumor progression in vivo, I generated MMTV-F635 transgenic mice which overproduce an infrared fluorescence protein specifically in the mammary epithelial cells. This allows me for the first time to monitor efficacy of treatment modalities longitudinally in mice.
Embedded wafer level ball grid array (eWLB) (2006)

Wafer level packaging is gaining tremendous interest throughout the semiconductor industry, due to advantages in cost and performance. We report an embedded device technology, which is based on a molded 200 mm reconfigured wafer. Our approach is a way around the restrictions of standard wafer level packages, like the number of I/Os possible at a given pitch. This allows us to establish a broad packaging platform based on wafer level processes. The core process of this technology is the encapsulation of silicon dice. We demonstrate that compression molding is a promising approach for the embedding of devices with respect to topology, adhesion and reliability properties. The new technology we present here is a competitive solution delivering reliable ball grid array (BGA) packages.
NAD(+)-dependent isoform of 11 beta-hydroxysteroid dehydrogenase. Cloning and characterization of cDNA from sheep kidney (1994)

11 beta-Hydroxysteroid dehydrogenase (11-HSD) catalyzes the conversion of cortisol to cortisone and corticosterone to 11-dehydrocorticosterone. This activity may be required to confer normal ligand specificity upon the mineralocorticoid receptor. Although an isozyme of 11-HSD was previously isolated from rat liver, a different isozyme is apparently expressed in mineralocorticoid target tissues. We isolated a sheep kidney cDNA clone encoding this isozyme by expression screening using Xenopus oocytes. The cDNA is 1.8 kilobase pairs in length and encodes a protein of 427 amino acid residues with a predicted M(r) of 46,700. When expressed in oocytes, this enzyme functions as an NAD(+)-dependent 11 beta-dehydrogenase with very high affinity for steroids, but it has no detectable reductase activity. It is 37% identical in amino acid sequence to an NAD(+)-dependent isozyme of 17 beta-hydroxysteroid dehydrogenase but only 20% identical to the NADP(+)-dependent liver isozyme of 11-HSD. It is expressed at high levels in the kidney and adrenal and at lower levels in the colon. The corresponding gene is present in a single copy in the sheep genome. In humans, this gene is a candidate locus for the syndrome of apparent mineralocorticoid excess, a form of hypertension postulated to result from 11-HSD deficiency in mineralocorticoid target tissues.
Sirtuin 1 Is Required for Antagonist-Induced Transcriptional Repression of Androgen-Responsive Genes by the Androgen Receptor (2007)

Androgen antagonists or androgen deprivation is a primary therapeutic modality for the treatment of prostate cancer. Invariably, however, the disease becomes progressive and unresponsive to androgen ablation therapy (hormone refractory). The molecular mechanisms by which the androgen antagonists inhibit prostate cancer proliferation are not fully defined. In this report, we demonstrate that sirtuin 1 (SIRT1), a nicotinamide adenosine dinucleotide-dependent histone deacetylase (HDAC) linked to the regulation of longevity, is required for androgen antagonist-mediated transcriptional repression and growth suppression. Androgen antagonist-bound androgen receptor (AR) recruits SIRT1 and nuclear receptor corepressor to AR-responsive promoters and deacetylates histone H3 locally at the prostate-specific antigen promoter. Furthermore, SIRT1 down-regulation by small interfering RNA or by pharmacological means increased the sensitivity of androgen-responsive genes to androgen stimulation, enhanced the sensitivity of prostate cancer cell proliferative responses to androgens, and decreased the sensitivity of prostate cancer cells to androgen antagonists. In this study, we demonstrate the ligand-dependent recruitment of a class III HDAC into a corepressor transcriptional complex and a necessary functional role for a class III HDAC as a transcriptional corepressor in AR antagonist-induced transcriptional repression. Collectively, these findings identify SIRT1 as a corepressor of AR and elucidate a new molecular pathway relevant to prostate cancer growth and approaches to therapy.
Two Naturally Occurring Variants of TAFI (Thr-325 and Ile-325) Differ Substantially with Respect to Thermal Stability and Antifibrinolytic Activity of the Enzyme (2002)

Thrombin-activable fibrinolysis inhibitor (TAFI) is a carboxypeptidase B-like zymogen that is activated to TAFIa by plasmin, thrombin, or the thrombin-thrombomodulin complex. The enzyme TAFIa attenuates clot lysis by removing lysine residues from a fibrin clot. Screening of nine human cDNA libraries indicated a common variation in TAFI at position 325 (Ile-325 or Thr-325). This is in addition to the variation at amino acid position 147 (Ala-147 or Thr-147) characterized previously. Thus, four variants of TAFI having either Ala or Thr at position 147 and either Thr or Ile at position 325 were stably expressed in baby hamster kidney cells and purified to homogeneity. The kinetics of activation of TAFI by thrombin/thrombomodulin were identical for all four variants; however, Ile at position 325 extended the half-life of TAFIa from 8 to 15 min at 37 degrees C, regardless of the residue at position 147. In clot lysis assays with thrombomodulin and the TAFI variants, or with pre-activated TAFI variants, the Ile-325 variants exhibited an antifibrinolytic effect that was 60% greater than the Thr-325 variants. Similarly, in the absence of thrombomodulin, the Ile-325 variants exhibited an antifibrinolytic effect that was 30-50% greater than the Thr-325 variants. In contrast, the variation at position 147 had little if any effect on the antifibrinolytic potential of TAFIa. The increased antifibrinolytic potential of the Ile-325-containing TAFI variants reflects the fact that these variants have an increased ability to mediate the release of lysine from partially degraded fibrin and suppress plasminogen activation. These findings imply that individuals homozygous for the Ile-325 variant of TAFI would likely have a longer lived and more potent TAFIa enzyme than those homozygous for the Thr-325 variant.
Single Molecule Conductance through Rigid Norbornylogous Bridges with Zero Average Curvature (2008)

A new homologous series of norbornylogous (NB) bridges has been synthesized in which the average curvature of the bridges is very small. The molecules are rigid and have two thiol moieties at each end to allow them to form self-assembled monolayers (SAMs) and to connect to two gold electrodes to form a molecular junction. The SAMs formed were characterized using electrochemistry to determine the surface coverage of molecules on gold surface and to provide an indication of the packing of the NB bridges while ellipsometry and X-ray photoelectron spectroscopy (XPS) were used to provide an indication of the SAM thickness and orientation. Single molecule conductance of NB bridges was measured as a function of the molecular length. The conductance was found to decrease exponentially with the length with a decay constant that is exactly correlated with photoelectron transfer and other studies at the multiple molecule level. The molecule−electrode contact resistance was determined and compared with that of related alkanedithiol molecular junctions.
Understanding the mechanisms of aromatase inhibitor resistance (2012)

Aromatase inhibitors (AIs) have a central role in the treatment of breast cancer; however, resistance is a major obstacle to optimal management. Evidence from endocrine, molecular and pathological measurements in clinical material taken before and after therapy with AIs and data from clinical trials in which AIs have been given as treatment either alone or in combination with other targeted agents suggest diverse causes for resistance. These include inherent tumour insensitivity to oestrogen, ineffective inhibition of aromatase, sources of oestrogenic hormones independent of aromatase, activation of signalling by non-endocrine pathways, enhanced cell survival and selection of hormone-insensitive cellular clones during treatment.
Mutilation of RNA phage Qβ virus‐like particles: from icosahedrons to rods (2000)

Icosahedral virus-like particles (VLPs) of RNA phage Qbeta are stabilized by four disulfide bonds of cysteine residues 74 and 80 within the loop between beta-strands F and G (FG loop) of the monomeric subunits, which determine the five-fold and quasi-six-fold symmetry contacts of the VLPs. In order to reduce the stability of Qbeta VLPs, we mutationally converted the amino acid stretch 76-ANGSCD-81 within the FG loop into the 76-VGGVEL-81 sequence. It led to production in Escherichia coli cells of aberrant rod-like Qbeta VLPs, along with normal icosahedral capsids. The length of the rod-like particles exceeded 4-30 times the diameter of icosahedral Qbeta VLPs.
DNA Footprinting with the Hydroxyl Radical (1991)

The Fenton reaction of iron(II) EDTA with hydrogen peroxide, performed in the presence of ascorbate ion, has proven to be useful as a probe of structure in DNA systems. Two aspects of this chemistry are discussed: the identity of the active DNA cleaving agent produced by this reagent, and the application of the Fenton reaction to the determination of the structure of the Holliday junction, the four-stranded DNA molecule that is a key intermediate in recombination. The cleavage pattern of the Holliday junction has pseudo-twofold symmetry, putting important constraints on possible structures.
Effect of Duration of Fixation on Quantitative Reverse Transcription Polymerase Chain Reaction Analyses (2002)

Increasingly, there is the need to analyze gene expression in tumor tissues and correlate these findings with clinical outcome. Because there are few tissue banks containing enough frozen material suitable for large-scale genetic analyses, methods to isolate and quantify messenger RNA (mRNA) from formalin-fixed, paraffin-embedded tissue sections are needed. Recovery of RNA from routinely processed biopsies and quantification by the polymerase chain reaction (PCR) has been reported; however, the effects of formalin fixation have not been well studied. We used a proteinase K-salt precipitation RNA isolation protocol followed by TaqMan quantitative PCR to compare the effect of formalin fixation for 24, 48, and 72 hours and for 1 week in normal (2), oral epithelial dysplasia (3), and oral squamous cell carcinoma (4) specimens yielding 9 fresh and 36 formalin-fixed samples. We also compared mRNA and protein expression levels using immunohistochemistry for epidermal growth factor receptor (EGFR), matrix metalloproteinase (MMP)-1, p21, and vascular endothelial growth factor (VEGF) in 15 randomly selected and routinely processed oral carcinomas. We were able to extract RNA suitable for quantitative reverse transcription (RT) from all fresh (9/9) and formalin-fixed (36/36) specimens fixed for differing lengths of time and from all (15/15) randomly selected oral squamous cell carcinoma. We found that prolonged formalin fixation (>48 h) had a detrimental effect on quantitative RT polymerase chain reaction results that was most marked for MMP-1 and VEGF but less evident for p21 and EGFR. Comparisons of quantitative RT polymerase chain reaction and immunohistochemistry showed that for all markers, except p21, there was good correlation between mRNA and protein levels. p21 mRNA was overexpressed in only one case, but protein levels were elevated in all but one tumor, consistent with the established translational regulation of p21. These results show that RNA can be reliably isolated from formalin-fixed, paraffin-embedded tissue sections and can produce reliable quantitative RT-PCR data. However, results for some markers are adversely affected by prolonged formalin fixation times.