gebhart/patrepeval huggingface dataset:
Abstract 3555: Anti-tumor activity of CAL-101, a potent selective inhibitor of the p110Δ isoform of PI3K, in models of human glioblastoma (2011)

Abstract Phosphatidylinositol 3-kinase (PI3K) activation and Akt phosphorylation play a pivotal role in cell proliferation and survival, transducing signals from several cell surface receptors through PI3K isoforms (designated p110α, β, Δ, and γ). Our previous research has elucidated a significant role of the PI3K p110Δ (PI3KΔ) isoform in hematologic malignancies. Aberrant upregulation of the PI3K/Akt pathway is a frequently observed defect in human malignancies, including glioblastoma, but the role of the PI3KΔ isoform, has not been systematically evaluated. Selective inhibition of PI3KΔ with the orally bioavailable investigational drug, CAL-101, offers the potential for targeting PI3KΔ as a therapeutic approach to glioblastoma while avoiding undesirable side effects associated with pan-inhibitors that broadly block PI3K isoforms in multiple cell types. CAL-101 potently inhibits PI3KΔ (with an EC50 of 65 nM in a whole-blood assay) and shows &amp;gt;200-fold selectivity over other Class I PI3K isoforms and no activity against Class II and III PI3K family members or other PI3K-related proteins, including mTOR and DNA-PK. We examined expression levels of PI3KΔ and constitutive pathway activation in a panel of glioma cell lines (LN18, LN229, SF-539, U87MG, U138MG, and U251). PI3KΔ was consistently expressed and was functionally active, inducing high basal levels of phosphorylated-Akt (pAkt) in all tested cell lines. Treatment with CAL-101 decreased p-Akt levels in all cell lines and also reduced phosphorylation of the downstream pathway target, S6. Furthermore, PI3KΔ inhibition with CAL-101 resulted in an accumulation of cells in G1 and a decrease in the S phase population. Consistent with the effects of CAL-101 on G1 cell-cycle arrest, immunoblotting showed a decrease in cyclin D1 levels. In mice bearing U87MG xenografts, in vivo PI3KΔ inhibition resulted in significant anti-tumor effects, delaying time to tumor progression (tumor volume of &amp;gt;1000 mm3) by 30 days (p&amp;lt;0.001). Taken together, these data suggest that PI3KΔ overexpression and heightened functional activity contribute to glioblastoma proliferation, and that selective targeting of PI3KΔ may offer a novel therapeutic approach for patients with central nervous system tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3555. doi:10.1158/1538-7445.AM2011-3555
Monoclonal antibodies to the p21 products of the transforming gene of Harvey murine sarcoma virus and of the cellular ras gene family (1982)

We have isolated eight rat lymphocyte-myeloma hybrid cell lines producing monoclonal antibodies that react with the 21,000-dalton transforming protein (p21) encoded by the v-ras gene of Harvey murine sarcoma virus (Ha-MuSV). These antibodies specifically immunoprecipitate both phosphorylated and non-phosphorylated forms of p21 from lysates of cells transformed by Ha-MuSV. All eight react with the products of closely related ras genes expressed in cells transformed by two additional sarcoma viruses (rat sarcoma virus and BALB sarcoma virus) or by a cellular Harvey-ras gene placed under the control of a viral promoter. Three of the antibodies also react strongly with the p21 encoded by the v-ras gene of Kirsten MuSV. These same three antibodies immunoprecipitate the predominant p21 species synthesized normally in a variety of rodent cell lines, including the p21 produced at high levels in 416B murine hemopoietic cells. This suggests that an endogenous gene closely related to Kirsten-ras is expressed in these cells. The monoclonal antibodies have been used to confirm two properties associated with p21; localization at the inner surface of the membrane of Ha-MuSV-transformed cells, assayed by immunofluorescence microscopy, and binding of guanine nucleotides.
Lactobacillli expressing llama VHH fragments neutralise Lactococcusphages (2007)

Lactobacilli were able to express functional VHH fragments in both a secreted and a cell surface form and reduced phage infection of lactococcal cells. Lactobacilli expressing llama heavy-chain antibody fragments represent a novel way to limit phage infection.
Use of lacZ fusions to delimit regulatory elements of the inducible divergent GAL1-GAL10 promoter in Saccharomyces cerevisiae. (1984)

We present the DNA sequence of a 914-base pair fragment from Saccharomyces cerevisiae that contains the GAL1-GAL10 divergent promoter, 140 base pairs of GAL10 coding sequence, and 87 base pairs of GAL1 coding sequence. From this fragment, we constructed four pairs of GAL1-lacZ and GAL10-lacZ fusions on various types of yeast plasmid vectors. On each type of vector, the fused genes were induced by galactose and repressed by glucose. The response of a GAL1-lacZ fusion to gal4 and gal80 regulatory mutations was similar to the response of intact chromosomal GAL1 and GAL10 genes. A set of deletions that removed various portions of the GAL10 regulatory sequences from a GAL10-CYC1-lacZ fusion was constructed in vitro. These deletions defined a relatively guanine-cytosine-rich region of 45 base pairs that contained sequences necessary for full-strength galactose induction and an adjacent guanine-cytosine rich 55 base pairs that contained sequences sufficient for weak induction.
Coded Aperture Imaging: Many Holes Make Light Work (1980)

A coded aperture camera is similar to a pinhole camera in that no reflecting or refracting optics are used to form an image. However, it is different due to the fact that the single opening of the conventional pinhole camera has been replaced with a pattern of holes which may number in the hundreds or thousands. The resulting image is the superposition of many individual pinhole images and must be unscrambled to be meaningful. The advantage of the coded aperture is that many more photons are collected in a given period of time, and hence the resulting decoded image is of higher quality than if a conventional single pinhole camera were used. An additional advantage lies in the ability to obtain three-dimensional depth information from a single view. This paper presents an overview of past coded aperture imaging efforts which include the use of Fresnel zone plates, random arrays, and nonredundant pinhole arrays. The theory underlying their use is presented as well as a review of the digital and optical methods used in decoding. Recent important advances in the field, such as the use of uniformly redundant arrays, are presented. Typical results from some of the above-mentioned systems are shown and discussed.
Recent advances and future developments in PGD (1999)

PGD has now been practised for a decade. The basic techniques currently used involve embryo biopsy, polymerase chain reaction (PCR) and fluorescent in situ hybridization (FISH). Recent advances in molecular diagnostic techniques have included the use of fluorescent PCR, multiplex PCR and whole genome amplification. For cytogenetic analysis, many centres are now using five or more chromosome probes to examine for chromosome abnormalities, sexing and aneuploidy. Future improvements in molecular diagnosis include the use of quantitative PCR, DNA fingerprinting and microarray technology. Developments in methods to analyse chromosomes from a single cell have included interphase chromosome conversion, which has already been clinically applied, and the use of comparative genomic hybridization, which is still being developed. These methods will hopefully enable more accurate and a greater number of diseases to be diagnosed at the single cell level.
Early induction of GAD65‐reactive Th2 response in type 1 diabetic children treated with alum‐formulated GAD65 (2010)

Treatment with GAD-alum in type 1 diabetic children induced an early T-helper 2 immune enhanced response to GAD(65), followed by a wider spectrum of cytokines at 3 and 9 months.
Guidelines for controlled trials of drugs in migraine: Third edition. A guide for investigators (2012)

International audience
Treatment of refractoriness to platelet transfusion by protein A column therapy (1993)

Ten thrombocytopenic patients (platelets < 10-24 x 10(9)/L) who were refractory to platelet transfusion were investigated for their responsiveness to staphylococcal protein A column therapy. Nine patients had previously been treated with steroids, intravenous immune globulin, and/or other forms of immunosuppressive therapy without improvement in their transfusion response. All patients were receiving multiple platelet transfusions without achieving 1-hour corrected count increments (CCIs) > or = 7500. Eight patients had antibodies that reacted with platelets and were directed against HLA class I antigens, ABO antigens, and/or platelet-specific alloantigens. Plasma (500-2000 mL) from each patient was passed over a protein A silica gel column and then returned to the patient. Patients received from 1 to 14 treatments. A positive response to protein A therapy was defined as at least a doubling of the pretreatment platelet count and/or two successive 10- to 120-minute posttransfusion CCIs > or = 7500. Following plasma treatments, 6 of 10 patients responded with daily platelet counts that averaged 48 +/- 11 x 10(9) per L as compared with counts of 16 +/- 7 x 10(9) per L (p < 0.0005) before treatment. Posttransfusion CCI values determined in four of these patients averaged 2480 +/- 810 and 10,010 +/- 3540 (p < 0.005) before and after treatment, respectively. In contrast, among the four unresponsive patients, platelet counts averaged 10 +/- 9 and 13 +/- 10 x 10(9) per L (p = NS), respectively, while posttransfusion CCIs were 700 +/- 1410 and 1520 +/- 2460 (p = NS), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
A New Technic for the Radium Treatment of Carcinoma of the Bladder (1949)

Treatment of cancer of the urinary bladder entails not only eradication of the primary tumor by methods tolerable to the patient, but also prevention of recurrent and new tumor growths. The high incidence of new growths following local resection, fulguration, or irradiation, and the necessity of relentlessly guarding against recurrence by periodic examination, are evidence of the inadequacy of the present methods of treatment. To meet these problems, a new radium technic was devised and first used at Walter Reed General Hospital on July 18, 1945. Favorable experience with the first 13 cases warrants this preliminary report. The Walter Reed technic entails isoirradiation of the lower two-thirds of the bladder wall with fractionated exposures of penetrative gamma rays from a focal source of radium, radon, or radioactive cobalt fixed at the center of the bladder cavity. With this procedure certain disadvantages of other methods of irradiation are circumvented. Interstitial irradiation with radium needles or radon implants often results in focal radionecrotic ulceration attended by intractable pain, fistula, and fibrosis. Surface application of radium through a cystoscope is inaccurate and ineffective. External irradiation with x-rays, especially supervoltage irradiation, is occasionally effective, but may injure the bladder and adjacent bowel, and is frequently followed by a fibrosed contracted bladder of small capacity. The Walter Reed Technic Preoperative Diagnosis and Delineation of the Tumor: It is first necessary to ascertain as accurately as possible the geometric size, location, and type of the tumor to be treated. This is done by cystoscopy, biopsy, and pyelography and cystography with an opaque medium or air. Radiographic examination should include anteroposterior and postero-anterior as well as lateral and oblique views of the bladder, for occasionally these may yield more information as to infiltration and extravesical extension than direct observation and palpation of the opened organ. Cystotomy: At the time of the first radium insertion, the bladder is opened by suprapubic cystotomy and the tumor carefully inspected and classified. A papillary tumor with a narrow pedicle is totally resected with scissors, and the mucosa is sutured (Fig. 1). A bulky papillary tumor with a pedunculated or broad base is removed by electrosurgery, care being taken to cut down to the base only and not into the bladder wall, leaving a flat, slightly elevated sessile base of partly coagulated tissue about 3 or 4 mm. thick. If coagulation is carried down to the level of or into the bladder wall, secondary infection plus subsequent irradiation will unduly retard healing and result in an indolent ulcer requiring several months to heal, attended by painful cystitis. If the tumor is flat or sessile (Case 8) coagulation is unnecessary.
Migrastatin and a New Compound, Isomigrastatin, from Streptomyces platensis. (2002)

Streptomyces platensis (strain NRRL 18993), a producer of dorrigocins, was shown to produce migrastatin, a cyclic congener of dorrigocin A previously reported from a different organism. Additionally a new compound isomeric to migrastatin, isomigrastatin, was also isolated and its structure was determined to be a cyclic form of dorrigocin B. Both compounds were fully characterized from MS and NMR data. Product titers of both were improved by the addition of XAD-16 resin to the fermentation medium.
Nonlinear control of an oil well (1997)

Recent studies of waterflood and steamdrive in petroleum reservoirs have revealed that unwanted extension of hydrofractures is caused primarily by aggressive actions taken by conventional PI or PID controllers during injector start-up, or by operating near hydrofracturing pressure. The extension has resulted in reservoir damage and irreversible lost oil production. In this paper, we consider CalResources Phase III steam injection pilot in the South Belridge field of California. For each injector in this pilot, a neural network model is identified by using historical data on injection-fluid flow rate, well-head pressure, depth to the top of perforation, and the length of perforated interval. Differential geometric well-head pressure controllers are synthesized by using the neural network models. The satisfactory performance of the neural network model-based controllers is demonstrated, via numerical simulations.
Fluorescent In Situ Hybridization Allows Rapid Identification of Microorganisms in Blood Cultures (2000)

Using fluorescent in situ hybridization (FISH) with rRNA-targeted fluorescently labelled oligonucleotide probes, pathogens were rapidly detected and identified in positive blood culture bottles without cultivation and biotyping. In this study, 115 blood cultures with a positive growth index as determined by a continuous-reading automated blood culture system were examined by both conventional laboratory methods and FISH. For this purpose, oligonucleotide probes that allowed identification of approximately 95% of those pathogens typically associated with bacteremia were produced. The sensitivity and specificity of these probes were 100%. From all 115 blood cultures, microorganisms were grown after 1 day and identification to the family, genus, or species level was achieved after 1 to 3 days while 111 samples (96.5%) were similarly identified by FISH within 2.5 h. Staphylococci were identified in 62 of 62 samples, streptococci and enterococci were identified in 19 of 20 samples, gram-negative rods were identified in 28 of 30 samples, and fungi were identified in two of two samples. Thus, FISH is an appropriate method for identification of pathogens grown in blood cultures from septicemic patients.
Fast motion planning for multiple moving robots (2003)

The author presents an efficient solution to the motion-planning problem for multiple translating robots in the plane. It is shown that careful priority assignment can greatly reduce the average running time of the planner. A priority assignment method is introduced which attempts to maximize the number of robots which can move in a straight line form their start point to their goal point, thereby minimizing the number of robots for which expensive collision-avoiding search is necessary. This prioritization method is extremely effective in sparse workspaces where the moving robots are the primary obstacle.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A Low‐Cost, High‐Throughput Polyacrylamide Gel Electrophoresis System for Genotyping with Microsatellite DNA Markers (2003)

Microsatellite DNA markers are widely used in genetic research. Their use, however, can be costly and throughput is sometimes limited. The objective of this paper is to introduce a simple, low‐cost, high‐throughput system that detects amplification products from microsatellite markers by nondenaturing polyacrylamide gel electrophoresis. This system is capable of separating DNA fragments that differ by as little as two base pairs. The electrophoresis unit holds two vertical 100‐sample gels allowing standards and samples from a 96‐well plate to be analyzed on a single gel. DNA samples are stained during electrophoresis by ethidium bromide in the running buffer. In addition, one of the gel plates is UV‐transparent so that gels can be photographed immediately after electrophoresis without disassembling the gel‐plate sandwich. Electrophoresis runs are generally less than two hours. The cost per gel, excluding PCR cost, is currently estimated at about $2.60, or less than $0.03 per data point. This system has been used successfully with soybean [ Glycine max (L.) Merr.] and wheat ( Triticum aestivum L.) microsatellite markers and could be a valuable tool for researchers employing markers in other species.
Health Care Resource Use and Costs of Two-Year Survivors of Acute Lung Injury. An Observational Cohort Study (2015)

In this multisite study of 138 two-year survivors of ALI, 80% had one or more inpatient admission, representing a median (IQR) estimated cost $35,259 ($10,565-$81,166) per patient and $6,598,766 for the entire cohort. Hospital readmissions represented 76% of total inpatient costs, and having Medicare or Medicaid before ALI was associated with increased costs. With the aging population and increasing comorbidity, these findings have important health policy implications for the care of critically ill patients.
Autograph: toward automated, distributed worm signature detection (2004)

Today's Internet intrustion detection systems (IDSes) monitor edge networks' DMZs to identify and/or filter malicious flows. While an IDS helps protect the hosts on its local edge network from compromise and denial of service, it cannot alone effectively intervene to halt and reverse the spreading of novel Internet worms. Generation of the worm signatures required by an IDS--the byte patterns sought in monitored traffic to identify worms--today entails non-trivial human labor, and thus significant delay: as network operators detect anomalous behavior, they communicate with one another and manually study packet traces to produce a worm signature. Yet intervention must occur early in an epidemic to halt a worm's spread. In this paper, we describe Autograph, a system that automatically generates signatures for novel Internet worms that propagate using TCP transport. Autograph generates signatures by analyzing the prevalence of portions of flow payloads, and thus uses no knowledge of protocol semantics above the TCP level. It is designed to produce signatures that exhibit high sensitivity (high true positives) and high specificity (low false positives); our evaluation of the system on real DMZ traces validates that it achieves these goals. We extend Autograph to share port scan reports among distributed monitor instances, and using trace-driven simulation, demonstrate the value of this technique in speeding the generation of signatures for novel worms. Our results elucidate the fundamental trade-off between early generation of signatures for novel worms and the specificity of these generated signatures.
MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib (2007)

In human lung adenocarcinomas harboring EGFR mutations, a second-site point mutation that substitutes methionine for threonine at position 790 (T790M) is associated with approximately half of cases of acquired resistance to the EGFR kinase inhibitors, gefitinib and erlotinib. To identify other potential mechanisms that contribute to disease progression, we used array-based comparative genomic hybridization (aCGH) to compare genomic profiles of EGFR mutant tumors from untreated patients with those from patients with acquired resistance. Among three loci demonstrating recurrent copy number alterations (CNAs) specific to the acquired resistance set, one contained the MET proto-oncogene. Collectively, analysis of tumor samples from multiple independent patient cohorts revealed that MET was amplified in tumors from 9 of 43 (21%) patients with acquired resistance but in only two tumors from 62 untreated patients (3%) (P = 0.007, Fisher's Exact test). Among 10 resistant tumors from the nine patients with MET amplification, 4 also harbored the EGFR(T790M) mutation. We also found that an existing EGFR mutant lung adenocarcinoma cell line, NCI-H820, harbors MET amplification in addition to a drug-sensitive EGFR mutation and the T790M change. Growth inhibition studies demonstrate that these cells are resistant to both erlotinib and an irreversible EGFR inhibitor (CL-387,785) but sensitive to a multikinase inhibitor (XL880) with potent activity against MET. Taken together, these data suggest that MET amplification occurs independently of EGFR(T790M) mutations and that MET may be a clinically relevant therapeutic target for some patients with acquired resistance to gefitinib or erlotinib.
High-peak-power pulsed fiber sources (2004)

We report on the effectiveness of bend-loss mode filtering for power scaling of large-core, rare-earth-doped fibers. The technique affords a diffraction-limited beam quality from multimode fibers, which is crucial for practical applications of fiber sources. We demonstrate the technique in a >300-kW-peak-power, <1-ns-pulse-duration Yb-doped fiber amplifier, which we used for multiple harmonic generation.
Genome Type Analysis of Adenovirus Types 3 and 7 Isolated during Successive Outbreaks of Lower Respiratory Tract Infections in Children (2003)

Adenovirus is an important cause of respiratory infections in infants and children. Fifty-one serotypes have been identified, and adenovirus type 3 (Ad3) and Ad7 have often been associated with outbreaks of severe respiratory tract infections. Each serotype can be further divided into genome types based on the patterns of digestion of their DNAs with restriction enzymes. DNA restriction analysis was performed with 56 strains of Ad3 and 98 strains of Ad7 by using 12 restriction enzymes recognizing 6 bp (BamHI, BclI, BglI, BglII, BstEII, EcoRI, HindIII, HpaI, SalI, SmaI, XbaI, and XhoI). The virus strains were isolated during outbreaks of lower respiratory tract infections in children during an 11-year period from 1990 to 2000 in Seoul, Korea. Among the Ad3 strains, seven genome types were identified; Ad3a and six novel types (Ad3a13, Ad3a14, Ad3a15, Ad3a16, Ad3a17, and Ad3a18). Multiple genome types cocirculated during outbreaks, and some of these were isolated during the 11-year observation period, while others were restricted to particular outbreaks. For Ad7, two genome types, Ad7d and Ad7l, the latter of which is a novel genome type, were identified. A shift in genome types occurred from Ad7d to Ad7l during successive outbreaks. Mortality was 3.6% among children with Ad3 infections and 18% among children infected with either of the Ad7 genome types. In conclusion, the data confirm that Ad3 genome types are more diverse than those of Ad7 and suggest that shifts of genome types may occur during successive outbreaks of Ad3 and Ad7.