gebhart/patrepeval huggingface dataset:
PF285 ZELLA‐101: PHASE 1 STUDY OF ALVOCIDIB FOLLOWED BY 7+3 INDUCTION IN NEWLY DIAGNOSED AML PATIENTS (2019)

Background: Alvocidib, a potent cyclin‐dependent kinase‐9 (CDK‐9) inhibitor, has been studied extensively in newly diagnosed and relapsed/refractory AML in a timed sequential combination with cytarabine and mitoxantrone (ACM) with promising activity. Inhibition of CDK‐9 leads to downregulation of BCL‐2 family member, MCL‐1, which in turn inhibits tumor growth. We hypothesized that alvocidib followed by 7+3 induction therapy would be safe and effective in newly diagnosed non‐favorable risk AML. Aims: To evaluate the safety and clinical activity of alvocidib, in combination with cytarabine and daunorubicin (7+3), in previously untreated AML Methods: We are conducting a multicenter, open‐label, dose‐escalation, safety and biomarker prediction study (Zella 101) of alvocidib given as timed sequential therapy prior to cytarabine and daunorubicin for adults with previously untreated AML. The key eligibility criteria are: ages 18–65 years; previously untreated AML; ECOG PS 0–2; and no major organ dysfunction. Treatment consisted of increasing dose levels of alvocidib starting at 20 mg/m 2 as a 30‐minute IV bolus followed by 30 mg/m 2 over 4 hours on days 1–3, cytarabine 100 mg/m 2 /day by continuous IV infusion on days 5–11, and daunorubicin 60 mg/m 2 IV on days 5–7. Dose escalation was assessed by standard 3+3 design. Reinduction therapy with alvocidib (same dose as induction) days 1–3, followed by cytarabine 100 mg/m 2 /day continuous IV days 5–9 and daunorubicin 45 mg/m 2 IV days 5–6 was recommended in patients with >10% and >5% cellularity and blasts, respectively. Results: A total of 13 patients have been enrolled to date with the median age of 59 years (Range: 31–65 years) (See Table 1). The maximum dose of alvocidib administered was 30 mg/m 2 as a 30‐minute IV bolus followed by 60 mg/m 2 over 4 hours on days 1–3 as previously given in prior studies. Overall, alvocidib was well tolerated. The most common NCI CTCAE ≥Grade 3 treatment emergent nonhematologic AEs noted in ≥3 patients in the safety population were device related infection (30.8%), diarrhea (30.8%) and lung infection (23.1%). Cytogenetics were reported on 7 patients, 5 were intermediate to high risk. Ten patients were evaluable with post baseline response assessments, two patients were too early for disease assessment, and one patient died prior to disease assessment due to septic shock. Nine of the 10 evaluable patients achieved CR (9/10, 90%). Summary/Conclusion: Alvocidib given as timed sequential therapy prior to cytarabine and daunorubicin (7+3) induction in newly diagnosed AML demonstrated an acceptable safety profile with an MTD (30 mg/m 2 IV bolus followed by 60 mg/m 2 infusion over 4 hours) similar to previously investigated timed sequential regimens of alvocidib. Future directions include a randomized phase 2 expansion comparing cytarabine and daunorubicin with or without preceding timed sequential alvocidib, and prospective BH3 profiling of AML patients. image
Index compression for information retrieval systems (2008)

Given the increasing amount of information that is available today, there is a clear need for Information Retrieval (IR) systems that can process this information in an efficient and effective way. Efficient processing means minimising the amount of time and space required to process data, whereas effective processing means identifying accurately which information is relevant to the user and which is not. Traditionally, efficiency and effectiveness are at opposite ends (what is beneficial to efficiency is usually harmful to effectiveness, and vice versa), so the challenge of IR systems is to find a compromise between efficient and effective data processing. This thesis investigates the efficiency of IR systems. It suggests several novel strategies that can render IR systems more efficient by reducing the index size of IR systems, referred to as index compression. The index is the data structure that stores the information handled in the retrieval process. Two different approaches are proposed for index compression, namely document reordering and static index pruning. Both of these approaches exploit document collection characteristics in order to reduce the size of indexes, either by reassigning the document identifiers in the collection in the index, or by selectively discarding information that is less relevant to the retrieval process by pruning the index.
Security implications of Network Address Translators (NATs) (2009)

This document analyzes the security implications of Network Address
Translators (NATs). It neither deprecates nor encourages the use of
NATs, but rather aims to raise awareness about their security
implications, and possible implementation approaches to improve their
security.
Fibrin Sealant: Past, Present, and Future: A Brief Review (2009)

The modern literature on fibrin sealant now exceeds 3000 articles and continues to expand. This brief review presents the history of this material, its present clinical use, and its future applications.
Oxidative dimerization of methane over BaCO3, SrCO3 and these catalysts promoted with alkali (1986)

The yield and selectivity for formation of C2hydrocarbons from CH4 and O2 were 18.2 and 48.4% respectively over 2 g of BaCO3 at 1073 K at a CH4 :O2 ratio of 2.0:1, whereas the yield and selectivity were 2.5 and 99.5% over SrCO3 at 973 K at a CH4:O2 ratio of 37.9 : 1.
ChemInform Abstract: SOME REACTIONS OF DIAZOMETHANE WITH POLYFLUOROAZAOLEFINS (1978)

Abstract Bei der Behandlung mit Diazomethan erhält man aus den perfluorierten Schiffschen Basen (I) über die Addukte (II) die Aziridine (III) und (IV) sowie ein Triazol (Vb).
SIMPLE CHAOTIC CIRCUIT USING CMOS RING OSCILLATORS (2004)

In this study, a chaotic circuit suitable for an integrated circuit is proposed. The circuit consists of two CMOS ring oscillators and a pair of diodes. By using a simplified model of the circuit, the mechanism of generating chaos is explained and the exact solutions are derived. The exact expressions of the Poincaré map and its Jacobian matrix make those possible to confirm the generation of chaos using the Lyapunov exponents and to investigate the related bifurcation phenomena.
Arriving at an anti-forensics consensus: Examining how to define and control the anti-forensics problem (2006)

There are no general frameworks with which we may analyze the anti-forensics situation. Solving anti-forensic issues requires that we create a consensus view of the problem itself. This paper attempts to arrive at a standardized method of addressing anti-forensics by defining the term, categorizing the anti-forensics techniques and outlining general guidelines to protect forensic integrity.
Induction of unfolded protein response during neuronal induction of rat bone marrow stromal cells and mouse embryonic stem cells (2009)

When we treated rat bone marrow stromal cells (rBMSCs) with neuronal differentiation induction media, typical unfolded protein response (UPR) was observed. BIP/GRP78 protein expression was time-dependently increased, and three branches of UPR were all activated. ATF6 increased the transcription of XBP1 which was successfully spliced by IRE1. PERK was phosphorylated and it was followed by eIF2alpha phosphorylation. Transcription of two downstream targets of eIF2alpha, ATF4 and CHOP/GADD153, were transiently up-regulated with the peak level at 24 h. Immunocytochemical study showed clear coexpression of BIP and ATF4 with NeuN and Map2, respectively. UPR was also observed during the neuronal differentiation of mouse embryonic stem (mES) cells. Finally, chemical endoplasmic reticulum (ER) stress inducers, thapsigargin, tunicamycin, and brefeldin A, dose-dependently increased both mRNA and protein expressions of NF-L, and, its expression was specific to BIP-positive rBMSCs. Our results showing the induction of UPR during neuronal differentiations of rBMSCs and mES cells as well as NF-L expression by ER stress inducers strongly suggest the potential role of UPR in neuronal differentiation.
The properties of integrated micro-electrodes for CMOS-compatible medical sensors (2002)

Platinum microelectrodes for invasive medical applications have been developed for blood conductivity sensors and for the detection of biopotentials. The electrodes are fabricated in a standard CMOS-technology with only one additional production step. They have been combined with analog and digital electronic components on a single silicon substrate with a size of 1/spl times/5 mm/sup 2/. The electrodes' impedance characteristics, noise performance and geometrical considerations have been analysed. Due to the close neighbourhood of sensing elements and signal conditioning, integrated microsystems using integrated electrodes show enhanced resolution and a good rejection from electromagnetic distortions.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
U.S. Productivity: Down, but Not Out (1994)

Productivity in the United States doesn't get much attention, maybe because the figures are so hard to interpret and use. But the subject is of more than academic interest. Until the '70s, it was taken as a given that the U.S. would experience rapid growth in productivity and that our international competitive position would accordingly benefit. The experience of the '70s and '80s has drawn that assumption into question. Not only did productivity during those two decades dip below trend, but much of the decline couldn't be explained by conventional methods. Reasons for the shortfall have a practical meaning. Productivity growth is necessary if living standards are to rise. Moreover, productivity gains are essential in improving our international competitive position. With the advant of the North American Free Trade Agreement and with the lowering of tariffs from implementation of the General Agreement on Tariffs and Trade, our international competitive position will become increasingly interwined with the domestic economy. Also, rising productivity blunts the inflationary impact of a rising economy by moderating the impact of rising labor costs. Wages and benefits make up about two-thirds of the corporate cost structure. Rising output per man hour is an offset to higher labor costs. In recent years, productivity growth has fallen below the 2.1% trend that held for much of this century. Productivity growth fell from 2.5% in the '60s to 1.9% in the '70s. Growth fell further to 0.7% in the '80s. Recently, there have been signs of resurgence. So far in the '90s, growth has been 1.6%. Since 1970, many of our major trading partners have enjoyed faster productivity growth than the U.S. For example, from 1970 to 1979, productivity in the United States grew about 1.9%. The comparable figure in the United Kingdom was 2.8%, a little over 4% in France, 4.5% in Germany, and slightly above 5% in Japan. These countries' growth rates slowed in the '80s, but so did the U.S. growth rate. As a result, our competitive position as measured by productivity gains, has declined steadily over the past two decades. A number of reasons have been advanced to account for the shortfall in U.S. productivity. First is the continuing shift toward the growth of the service sector in the United States. Productivity growth is very difficult to achieve in service industries. In fact, it appears that productivity has actually fallen in some of these industries. Second is the impact of the postwar baby boom--people born from 1946 to 1965. The average age of the working population declined as baby-boomers entered the labor force beginning in the late '60s. …
Correlation of multidrug resistance (MDR1) protein expression with functional dye/drug efflux in acute myeloid leukemia by multiparameter flow cytometry: identification of discordant MDR-/efflux+ and MDR1+/efflux- cases (1995)

Resistance to chemotherapy is a major factor limiting successful treatment of acute myeloid leukemia (AML); one of the best characterized drug resistance mechanisms is extrusion of drugs by the energy-dependent multidrug resistance (MDR1) transport protein. Expression of MDR1 is common in AML and has been linked to lower remission induction rates and decreased remission durations. Because MDR1 efflux function may be modified by drugs such as cyclosporin A, accurate identification of MDR1+/efflux+ AML cases will be critical to identify patients who may benefit from therapies that contain such MDR1 modulators. We have optimized single and multiparameter flow cytometric assays to detect efflux of drugs or fluorescent dyes by previously cryopreserved AML blasts. These assays allowed precise identification of efflux by leukemic blasts, and correlation with CD34 and MDR1 expression. We subsequently studied a series of 60 previously untreated AML cases. Functional efflux was identified in 39 cases and was significantly correlated with MDR1 expression (P = .0002). However, discrepant cases were identified; 10 cases were efflux+ without significant MDR1 expression, whereas 6 MDR1+ cases were efflux-. There was also a highly significant correlation of efflux with CD34; 31 (79%) of the 39 efflux+ cases were CD34+ in comparison with only 5 (24%) of the 21 efflux- cases (P < .0001). Multivariate analysis showed that efflux was significantly associated with independent effects of both CD34 (P = .0011) and MDR1 expression (P = .034); the majority of efflux+ cases were CD34+, whereas 5 of the 6 MDR1+ efflux- cases lacked CD34 expression. Cyclosporin A blocked efflux in all but 2 cases regardless of MDR1 expression. Functional efflux in AML is frequently detected without the classic MDR1+ phenotype indicating that alternate non-MDR1-mediated efflux mechanisms may be important. Efflux assays may better identify patients who would benefit from therapies that include efflux modulators.
Estimates of ventilation from body surface measurements in unrestrained subjects (1986)

To make estimates of ventilation from measurements of body surface movements in unrestrained subjects, we measured changes in linear dimensions and cross-sectional areas of the rib cage (RC) and abdomen (AB) of six healthy unrestrained subjects during a variety of maneuvers. RC and AB anteroposterior diameters and abdominal length in the cephalocaudal axis (axial displacement) were measured with magnetometers, and RC and AB cross-sectional areas were measured with a respiratory inductance plethysmograph. Flow was measured at the mouth with a pneumotachograph and integrated electrically to give volume. Volume and body surface measurements were analyzed by multiple linear regression. Addition of the axial measurements to either the anteroposterior dimensions or cross-sectional areas of RC and AB improved estimates of tidal volume in all subjects (P less than 0.01). With measurements of axial displacement and cross-sectional area of the RC and AB, tidal volume could be reliably estimated to within 20% of actual ventilation. We conclude that measurement of axial displacements improves estimates of ventilation in unrestrained subjects.
Chlorzoxazone is metabolized by human CYP1A2 as well as by human CYP2E1 (1995)

Chlorzoxazone, a muscle-relaxing drug, is metabolized by carbon-hydroxylation at position 6. Chlorzoxazone has been suggested as an in vivo probe for CYP2E1. We studied the specificity of such a substrate using vaccinia virus expressed human P450 forms and the effect of inhibitors for chlorzoxazone metabolism by human liver microsomes. The 6-hydroxylation of chlorzoxazone was mediated by CYP1A2 as well as by CYP2E1. The Km value of CYP1A2 and CYP2E1 for the reaction was 5.69 microM and 232 microM, respectively. However, the Vmax value of CYP2E1 for the reaction was approximately 8.5-fold higher than that of CYP1A2. The CYP1A inhibitor, alpha-naphthoflavone, as well as the CYP2E1 inhibitor, diethyldithiocarbamate, decreased chlorzoxazone 6-hydroxylation at a low substrate concentration by human liver microsomes. Our results raise questions about the suitability of chlorzoxazone as an in vivo probe for hepatic CYP2E1 activity. In human liver microsomal samples, the Km = 40 microM was different from either the Km of CYP1A2 or CYP2E1. We think that this discrepancy is due to the co-expression of similar levels of CYP1A2 and CYP2E1 in human liver. Furthermore, it is suggested that the role of CYP2E1 in 6-hydroxychlorzoxazone formation at the physiological chlorzoxazone concentration of 30-60 microM is almost the same when compared to that of CYP1A2.
Racial Discrimination and Violence: A Longitudinal Perspective (2003)

A century ago, W. E. B. Du Bois wrote: "Crime is a phenomenon of organized social life, and is the open rebellion of an individual against his social environment" (1899/1996: 235). Explaining crime among blacks in Philadelphia between 1835 and 1895, Du Bois noted their overrepresentation in the courts as well as prisons and was acknowledging the damage to society done by racial discrimination both before and after the Civil War. Enumerations of prison populations in 1904, 1910, and 1923 showed serious overrepresentation of blacks both among resident prisoners and among those committed during the years of enumeration (Reuter, 1927). The fact that rates were higher for population counts than for intakes showed that blacks not only were convicted relatively more frequently but that, also, they were given longer sentences.
Pilot study of a novel tool for input‐free automated identification of transition zone prostate tumors using T2‐ and diffusion‐weighted signal and textural features (2013)

Purpose To present results of a pilot study to develop software that identifies regions suspicious for prostate transition zone (TZ) tumor, free of user input. Materials and Methods Eight patients with TZ tumors were used to develop the model by training a Naïve Bayes classifier to detect tumors based on selection of most accurate predictors among various signal and textural features on T2‐weighted imaging (T2WI) and apparent diffusion coefficient (ADC) maps. Features tested as inputs were: average signal, signal standard deviation, energy, contrast, correlation, homogeneity and entropy (all defined on T2WI); and average ADC. A forward selection scheme was used on the remaining 20% of training set supervoxels to identify important inputs. The trained model was tested on a different set of ten patients, half with TZ tumors. Results In training cases, the software tiled the TZ with 4 × 4‐voxel “supervoxels,” 80% of which were used to train the classifier. Each of 100 iterations selected T2WI energy and average ADC, which therefore were deemed the optimal model input. The two‐feature model was applied blindly to the separate set of test patients, again without operator input of suspicious foci. The software correctly predicted presence or absence of TZ tumor in all test patients. Furthermore, locations of predicted tumors corresponded spatially with locations of biopsies that had confirmed their presence. Conclusion Preliminary findings suggest that this tool has potential to accurately predict TZ tumor presence and location, without operator input. J. Magn. Reson. Imaging 2014;40:301–305 © 2013 Wiley Periodicals, Inc .
Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus. (1993)

Endothelium-dependent vasodilation is abnormal in forearm resistance vessels of patients with insulin-dependent diabetes mellitus. This abnormality may be relevant to the high prevalence of vascular disease that occurs in these individuals.
Predictive model building across different process conditions and shapes in 3D printing (2016)

Predictive models for geometric shape deformation constitute an important component in geometric fidelity control for three-dimensional (3D) printing. However, model building is made difficult by the wide variety of possible process conditions and shapes. A methodology that can make full use of data collected on different shapes and conditions, and reduce the haphazard aspect of traditional statistical model building techniques, is necessary in this context. We develop a new Bayesian procedure based on the effect equivalence and modular deformation features concepts that incorporates all available data for the systematic construction of predictive deformation models. Our method is applied to dramatically facilitate modeling of the multiple deformation profiles that exist in flat cylinders with different types of cavities. Ultimately, our Bayesian approach connects different process conditions and shapes to provide a unified framework for geometric fidelity control in 3D printing.
Anandamide, an Endogenous Cannabinoid, Inhibits Shaker-related Voltage-gated K+ Channels (1996)

Anandamide has been identified in porcine brain as an endogenous cannabinoid receptor ligand and is believed to be a counterpart to the psychoactive component of marijuana, delta 9-tetrahydrocannabinol (delta 9-THC). Here we report that anandamide directly inhibits (IC50, 2.7 muM) Shaker-related Kv1.2 K+ channels that are found ubiquitously in the mammalian brain. Delta 9-THC also inhibited Kv1.2 channels with comparable potency (IC50, 2.4 muM), as did several N-acyl-ethanolamides with cannabinoid receptor binding activity. Potassium current inhibition occurred through a pertussis toxin-insensitive mechanism and was not prevented by the cannabinoid receptor antagonist SR141716A. Utilizing excised patches of Kv1.2 channel-rich membrane as a rapid and sensitive bioassay, we found that phospholipase D stimulated the release of an endogenous anandamide-like K+ channel blocker from rat brain slices. Structure-activity studies were consistent with the possibility that the released blocker was either anandamide or another N-acyl-ethanolamide.
Evaluation de l'impact des projets de developpement sur la pauvrete (2002)

Very little is known about the actual impact of projects on the poor. Many are reluctant to carry out impact evaluations because they are deemed expensive, time consuming, and technically complex, and because the findings can be politically sensitive. Yet a rigorous evaluation can be powerful in assessing the appropriateness and effectiveness of programs. Evaluating impact is particularly critical in developing where resources are scarce and every dollar spent should aim to maximize its impact on poverty reduction. This handbook seeks to provide project managers and policy analysts with the tools needed for evaluating project impact. It is aimed at readers with a general knowledge of statistics. Chapter 1 presents an overview of concepts and methods, Chapter 2 discusses key steps and related issues to consider in implementation, Chapter 3 illustrates various analytical techniques through a case study, and Chapter 4 includes a discussion of lessons that have been reviewed for this handbook. The case studies, included in Annex I, were selected from a range of evaluations carried out by the Bank, other donor agencies, research institutions, and private consulting firms. Also included in the annexes are samples of the main components that would be necessary in planning any impact evaluation - sample terms of reference, a budget, impact indicators, a log frame, and a matrix of analysis.