gebhart/patrepeval huggingface dataset:
Physiological effects of a bactericidal protein from human polymorphonuclear leukocytes on Pseudomonas aeruginosa (1986)

The physiological changes seen in Pseudomonas aeruginosa after exposure to a bactericidal protein (BP) from the granules of human polymorphonuclear leukocytes were studied. It was demonstrated, using radiolabeled proline or leucine, that both the rate of cellular uptake and amino acid incorporation into trichloroacetic acid-insoluble material were markedly decreased immediately after exposure to BP. The rate of O2 consumption by P. aeruginosa was decreased immediately after exposure to BP and continued to decline exponentially until it ceased completely 30 min after exposure to BP. In the presence of 30 mM CaCl2 or MgCl2, bacteria were protected from death due to BP and respiration rates were unaffected. The cellular ATP pool of P. aeruginosa remained constant for up to 2 h after exposure to BP. Membrane depolarization was measured by the influx of the lipophilic anion thiocyanate. It was shown that the cytoplasmic membrane of P. aeruginosa was partially depolarized after exposure to BP. Purified BP killed 95% of 5 X 10(6) CFU of P. aeruginosa at a concentration of 60 to 100 ng of protein per ml. Although the concentration of bacteria and BP varied with each type of experiment, the BP/bacteria ratio required to cause a 95 to 99% loss in viability remained constant. We propose that cytoplasmic membrane depolarization is the biochemical lesion responsible for the other physiological changes seen and ultimately for the death of P. aeruginosa induced by BP.
In vitro drug sensitivity testing in human gliomas (1987)

In vitro drug sensitivity assays have been developed with the goal of predicting the clinical response to chemotherapy. The colony-forming assay, radiolabeled precursor inhibition assay, and microcytotoxicity assay are most commonly used. In retrospective studies, the assays correctly predict clinical response to a chemotherapeutic agent in 50% to 70% of patients and predict clinical resistance in nearly 100% of patients. All of the assays suffer from technical and theoretical problems. In vitro assays depend on cell culture and therefore do not entirely simulate in vivo conditions. Heterogeneity in chemosensitivity is commonly found and can complicate the interpretation of results. Further investigation is needed to determine if these assays will be able to select prospective chemotherapy for patients. The malignant origin of the cells in culture must be verified if meaningful conclusions are to be made.
X-linked inhibitor of apoptosis (XIAP) blocks Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis of prostate cancer cells in the presence of mitochondrial activation: sensitization by overexpression of second mitochondria-derived activator of caspase/direct IAP-binding protein with low pl (Smac/DIABLO). (2002)

The resistance to Apo2 ligand (Apo2L)/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis could be overcome by treatment with subtoxic concentrations of actinomycin D (Act D) in prostate tumor cells. Furthermore, the sensitization to Apo2L/TRAIL-mediated apoptosis by Act D positively correlated with selective down-regulation of X-linked inhibitor of apoptosis (XIAP). In this study, we examined whether second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pl (Smac/DIABLO), a known inhibitor of apoptosis (IAP)-neutralizing protein, sensitizes resistant prostate tumor cells to Apo2L/TRAIL-mediated apoptosis. The prostate tumor cell line CL-1 was treated with Apo2L/TRAIL, Act D, or a combination of the two. The apoptosis-mediated signaling pathway was examined by Western blotting and flow cytometry. Furthermore, CL-1 cells transfected with the anti-IAP inhibitor Smac/DIABLO were examined for sensitivity to Apo2L/TRAIL. Whereas Apo2L/TRAIL induced the release of cytochrome c and endogenous Smac/DIABLO in the CL-1 tumor cells, the cytosolic levels of both molecules were not sufficient to induce apoptosis. Transient transfectants with a Smac/DIABLO cDNA encoding a neutralizing inhibitor of IAPs were sensitized to Apo2L/TRAIL-mediated apoptosis. The sensitization to Apo2L/TRAIL by Smac/DIABLO overexpression was a result of synergistic activation of caspases-3, -9, and -8. Treatment of the Smac/DIABLO transient transfectant with Apo2L/TRAIL enhanced the release of Smac/DIABLO from mitochondria and led to reduction of IAP family proteins (XIAP, c-IAP1, and c-IAP2). These results show that Smac/DIABLO can sensitize CL-1 tumor cells to Apo2L/TRAIL-mediated apoptosis. Thus, up-regulation of Smac/DIABLO and sensitization to Apo2L/TRAIL-mediated apoptosis are of potential clinical application in the immunotherapy of drug-/Apo2L/TRAIL-resistant tumors.
Adenovirus-Mediated p53 Gene Therapy for Human Cancer (2000)

Recent advances in molecular biology have fostered remarkable insights into the molecular basis of neoplasms. Considerable evidence has accumulated that among the mechanisms of human cancer development are overexpression of dominant oncogenes, expression of mutant oncogenes, or specific chromosomal deletions or mutations that induce inactivation of tumor-suppressor genes. This understanding of cancer pathogenesis suggests that restoration of the function of critical gene products could halt or reverse these abnormalities, thus having a therapeutic effect. The p53 tumor suppressor gene has been implicated in many inherited and sporadic forms of malignancies in humans. Preclinical experiments have demonstrated that restoration of wildtype p53 function in the cancer cell by gene transfer is sufficient to cause antitumor effects such as cell-cycle arrest and induction of apoptosis. This approach has entered clinical testing and provided intriguing information about the intratumoral administration of an adenovirus vector expressing the wildtype p53 gene in non-small-cell lung cancer. The clinical study has also provided evidence of the bystander phenomenon, which is important for potential clinical efficacy. This article reviews recent highlights in this rapidly evolving field: p53 gene therapy for human cancer.
Glancing angle deposition: Fabrication, properties, and applications of micro- and nanostructured thin films (2007)

Physical vapor deposition under conditions of obliquely incident flux and limited adatom diffusion results in a film with a columnar microstructure. These columns will be oriented toward the vapor source and substrate rotation can be used to sculpt the columns into various morphologies. This is the basis for glancing angle deposition (GLAD), a technique for fabricating porous thin films with engineered structures. The origin of the columnar structure characteristic of GLAD films is discussed in terms of nucleation processes and structure zone models. As deposition continues, the columnar structures are influenced by atomic-scale ballistic shadowing and surface diffusion. Competitive growth is observed where the tallest columns grow at the expense of smaller features. The column shape evolves during growth, and power-law scaling behavior is observed as shown in both experimental results and theoretical simulations. Due to the porous nature of the films and the increased surface area, a variety of chemical applications and sensor device architectures are possible. Because the GLAD process provides precise nanoscale control over the film structure, characteristics such as the mechanical, magnetic, and optical properties of the deposited film may be engineered for various applications. Depositing onto prepatterned substrates forces the columns to adopt a planar ordering, an important requirement for photonic crystal applications.
A mutation in periaxin is responsible for CMT4F, an autosomal recessive form of Charcot-Marie-Tooth disease (2001)

Charcot-Marie-Tooth (CMT) disease is a heterogeneous group of inherited peripheral motor and sensory neuropathies characterized by chronic distal weakness with progressive muscular atrophy and sensory loss in the distal extremities. Inheritance can be autosomal dominant, X-linked or autosomal recessive (ARCMT). Recently, a locus responsible for a demyelinating form of ARCMT disease, named CMT4F, has been mapped on 19q13 in a large consanguineous Lebanese family. L- and S-periaxin are proteins of myelinating Schwann cells and homozygous periaxin-null mice display extensive demyelination of myelinated fibers in the peripheral nervous system, which suggests that the periaxin gene is a good candidate gene for an ARCMT disease. The human gene encoding the periaxins (PRX) was mapped to 19q13, in the CMT4F candidate interval. After characterizing the human PRX gene, we identified a nonsense R196X mutation in the Lebanese family which cosegregated with CMT. Histopathological and immunohistochemical analysis of a sural nerve biopsy of one patient revealed common features with the mouse mutant and the absence of L-periaxin from the myelin sheath. These data confirm the importance of the periaxin proteins to normal Schwann cell function and substantiate the utility of the periaxin-null mouse as a model of ARCMT disease.
Circulating Cell-Free DNA in Plasma/Serum of Lung Cancer Patients as a Potential Screening and Prognostic Tool (2006)

The findings from the studies on serum/plasma DNA suggest that it would be possible to develop a simple blood test with high sensitivity and specificity that has potential for screening of high-risk individuals, for prognostic or staging purposes, and to be used as intermediate end-points of efficacy in chemo-prevention and therapeutic trials. However, further work is needed to identify additional biomarkers and to standardize present techniques for sample collection, processing, and analysis. Large prospective studies with long follow-ups are essential to eventually integrate blood marker-based assays into the clinical setting.
The Barriers to Electronic Medical Record Systems and How to Overcome Them (1997)

Institutions all want electronic medical record (EMR) systems. They want them to solve their record movement problems, to improve the quality and coherence of the care process, to automate guidelines and care pathways to assist clinical research, outcomes management, and process improvement. EMRs are very difficult to construct because the existing electronic data sources, e.g., laboratory systems, pharmacy systems, and physician dictation systems, reside on many isolated islands with differing structures, differing levels of granularity, and different code systems. To accelerate EMR deployment we need to focus on the interfaces instead of the EMR system. We have the interface solutions in the form of standards: IP, HL7/ASTM, DICOM, LOINC, SNOMED, and others developed by the medical informatics community. We just have to embrace them. One remaining problem is the efficient capture of physician information in a coded form. Research is still needed to solve this last problem.
Enantioselective Synthesis of 2-Aryl-4-piperidones via Rhodium/Phosphoramidite-Catalyzed Conjugate Addition of Arylboroxines (2005)

[reaction: see text] The highly enantioselective synthesis of 2-aryl-4-piperidones by rhodium/phosphoramidite-catalyzed conjugate addition of arylboroxines to 2,3-dihydro-4-pyridones is described. Both enantiomers of a variety of products with sterically and electronically different R substituents were obtained in high isolated yield and with excellent enantioselectivity up to 99%.
Как измеряются эффективность и «продуктивность» (1999)

Статья поднимает проблему оценка деятельности школы. По традиции начальное и среднее образование во Франции ос­таются сектором преимущественно государствен­ной деятельности. Иногда, правда, выдвигались идеи приватизации школы, но они никогда не получали широкой поддержки. Другое дело, как именно, на основании каких показателей измерить эффективность и «продуктивность, школы?
A Multivariate Logistic Regression Equation to Screen for Diabetes (2002)

This multivariate logistic equation improves on currently recommended methods of screening for undiagnosed diabetes and can be easily implemented in a inexpensive handheld programmable calculator to predict previously undiagnosed diabetes.
Innate antiviral response targets HIV-1 release by the induction of ubiquitin-like protein ISG15 (2006)

The goal of this study was to elucidate the molecular mechanism by which type I IFN inhibits assembly and release of HIV-1 virions. Our study revealed that the IFN-induced ubiquitin-like protein ISG15 mimics the IFN effect and inhibits release of HIV-1 virions without having any effect on the synthesis of HIV-1 proteins in the cells. ISG15 expression specifically inhibited ubiquitination of Gag and Tsg101 and disrupted the interaction of the Gag L domain with Tsg101, but conjugation of ISG15 to Gag or Tsg101 was not detected. The inhibition of Gag-Tsg101 interaction was also detected in HIV-1 infected, IFN-treated cells. Elimination of ISG15 expression by small interfering RNA reversed the IFN-mediated inhibition of HIV-1 replication and release of virions. These results indicated a critical role for ISG15 in the IFN-mediated inhibition of late stages of HIV-1 assembly and release and pointed to a mechanism by which the innate antiviral response targets the cellular endosomal trafficking pathway used by HIV-1 to exit the cell. Identification of ISG15 as the critical component in IFN-mediated inhibition of HIV-1 release advances the understanding of the IFN-mediated inhibition of HIV-1 replication and uncovers a target for the anti HIV-1 therapy.
SunSine300 AC module. Annual report, July 25, 1995--December 31, 1996 (1997)

Under Photovoltaic Manufacturing Technology (PVMaT) 4A1, Ascension Technology (AT) is developing the SunSine300 AC PV module. AT`s goals in this project are to meet Underwriters Laboratory (UL) 1741 requirements, obtain Federal Communications Commission (FCC) Class B verification, complete the AC module system design and development, advance the inverter design, design for manufacture, design for reliability, design for serviceability, and demonstrate commercialization through production and sale of about 100 units. To meet these goals, AT corrected a number of deficiencies identified by UL`s preliminary investigation before proceeding to the full UL investigation; a SunSine300 prototype was tested and found to comply with FCC Class B requirements; AT designed a complete line of balance-of-systems hardware for the SunSine 300; AT`s design and performance advancements include accomplishing a total harmonic distortion drop from 5% to 2%, devising a method to eliminate false detection of zero crossings that could damage the inverter, improving the anti-islanding with the addition of AT`s proprietary ZEBRA technique, and redesigning the enclosure for thermal performance, manufacturability, and UL and FCC approval; performing extensive testing in Phase 2 to discover failure modes and susceptibility to aging; and designing the SunSine300 to be easily and safely serviced. 3 figs., 3 tabs.
Translational Mini-Review Series on Toll-like Receptors:&#x2028;Toll-like receptor ligands as novel pharmaceuticals for allergic disorders (2007)

Characterization of the Toll-like receptor (TLR) family and associated signalling pathways provides a key molecular basis for our understanding of the relationship between exposure to microbial products and susceptibility to immune-mediated disorders. Indeed, ligation of TLR controls innate and adaptive immune responses by inducing synthesis of pro- as well as anti-inflammatory cytokines and activation of effector as well as regulatory lymphocytes. TLRs are therefore considered as major targets for the development of vaccine adjuvants, but also of new immunotherapies. Herein, we review the potential of TLR ligands as a novel class of pharmaceuticals for the prevention or treatment of allergic disorders.
Ultrarapid Generation of Femtoliter Microfluidic Droplets for Single-Molecule-Counting Immunoassays (2013)

We report a microfluidic droplet-based approach enabling the measurement of chemical reactions of individual enzyme molecules and its application to a single-molecule-counting immunoassay. A microfluidic device is used to generate and manipulate <10 fL droplets at rates of up to 1.3 × 10(6) per second, about 2 orders of magnitude faster than has previously been reported. The femtodroplets produced with this device can be used to encapsulate single biomolecular complexes tagged with a reporter enzyme; their small volume enables the fluorescent product of a single enzyme molecule to be detected within 10 min of on-chip incubation. Our prototype system is validated by detection of a biomarker for prostate cancer in buffer, down to a concentration of 46 fM. This work demonstrates a highly flexible and sensitive diagnostic platform that exploits extremely high-speed generation of monodisperse femtoliter droplets for the counting of individual analyte molecules.
Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines (1998)

Oral administration of DSS has been reported to induce an acute and chronic colitis in mice. The aim of our study was to evaluate if the chronic phase of DSS-induced colitis was characterized by a Th1/Th2 response and how this would relate to mucosal regeneration. Swiss Webster mice were fed 5% DSS in their drinking water for 7 days, followed by 2-5 weeks consumption of water. Control mice received only water. The animals were killed at 3 and 6 weeks after induction. Their colons were isolated for histology and immunohistochemistry, using specific MoAbs for T and B cells, macrophages, interferon-gamma (IFN-gamma), IL-4 and IL-5. Colons were scored for inflammation, damage and regeneration. Two weeks after stopping DSS the colonic epithelium had only partially healed. Total colitis scores were still increased, especially in the distal colon, which was due to more inflammation, damage and less regeneration. In areas of incomplete colonic healing the basal parts of the lamina propria contained macrophages and CD4+ T cells. These CD4+ T cells showed a focal increase of IFN-gamma and IL-4 staining compared with control animals. These findings were still observed 5 weeks after stopping DSS in some mice, albeit less extensive. Chronic DSS-induced colitis is characterized by focal epithelial regeneration and a Th1 as well as Th2 cytokine profile. We postulate that chronic immune activation mediated by both populations of Th cells can interfere with colonic healing and can play a role in the pathogenesis of chronic colitis.
Preliminary findings from a phase I, multicenter, open-label study of the anti-CD37 antibody-drug conjugate (ADC), IMGN529, in adult patients with relapsed or refractory non-Hodgkin lymphoma (NHL). (2014)

8526 Background: IMGN529 is a CD37-targeting ADC comprising a CD37-binding antibody conjugated to the maytansinoid anti-mitotic, DM1. CD37 is present on the surface of normal and malignant B lymphocytes. In preclinical studies, IMGN529 exhibits potent antitumor activity against NHL cells via direct inhibition, effector function and delivery of the maytansinoid payload. Methods: Study objectives are: determine the maximum tolerated dose/recommended phase 2 dose of IMGN529 in adult patients (pts) with relapsed or refractory NHL, and evaluate safety, pharmacokinetics, pharmacodynamics, and evidence of preliminary efficacy. IMGN529 is given intravenously on Day (d) 1 of each 21d cycle (C). Results: To date, 22 pts have been enrolled across four dose levels ranging from 0.1 to 0.8 mg/kg. NHL subtypes enrolled: 10 Follicular lymphoma (FL), 7 Diffuse large B-cell (DLBCL), 5 other. A reduction in lymphocyte count seen early after dosing (d 2) in the majority of pts suggests a CD37-mediated reduction in lymphocytes. One pt with DLBCL treated at 0.4 mg/kg, and 1 pt with FL treated at 0.2 mg/kg achieved partial remission in C 3 and C 5 respectively. Dose limiting toxicities (DLTs) consisted of grade (G) 4 neutropenia > 7 days (1pt) and G2 peripheral neuropathy (1pt) at 0.8 mg/kg and G3 febrile neutropenia (2 pts) at 0.4 mg/kg. Adverse events (AEs) of G3 or higher occurred in 8 pts; those reported in more than 1 pt were: neutropenia (5 pts) and febrile neutropenia (2pts). Four of these pts experienced transient, early onset (C1d2-4) G3 neutropenia which may be a manifestation of cytokine release. The protocol was amended to provide peri-infusional steroids as a prophylactic regimen and dose re-escalation is ongoing; 3 patients treated at 0.4 mg/kg have completed C 1 with no DLTs. Clinical trial enrollment is ongoing with additional data expected. Preclinical studies to investigate the mechanism of the transient neutropenia are underway. Conclusions: IMGN529, a CD37-targeting ADC, has demonstrated early evidence of clinical activity and has the potential to be a novel therapeutic for B-cell lymphoproliferative malignancies. Clinical trial information: 01534715.
Rearrangement and expression of T-cell antigen receptor genes in human T-lymphocyte tumor lines and normal human T-cell clones: evidence for allelic exclusion of Ti beta gene expression and preferential use of a J beta 2 gene segment. (1986)

The gene encoding the beta chain of the human T-cell receptor for antigen is composed of variable (V), diversity (D), joining (J), and constant (C) gene segments which undergo specific rearrangements during T-lymphocyte ontogeny. Southern blot analyses of seven human T-cell tumor lines and normal human T-lymphocyte clones revealed that most of these T-cell lines rearrange their Ti beta genes differently. The T-cell tumor line HPB-MLT rearranges and transcribes both of its Ti beta genes. Cloning and sequencing of the Ti beta cDNAs corresponding to these rearrangements revealed that one of the rearranged Ti beta genes is defective, while the other is functional and corresponds to the Ti beta protein expressed on the surface of these cells. Thus, this cell line displays a pattern of allelic exclusion of Ti beta gene expression. A comparison of four C beta 2-containing Ti beta cDNAs from three different cell lines revealed that three of the four utilize the same J beta 2.5 gene segment joined to different D beta and V beta genes, suggesting that there may be preferential use of this J gene during J beta 2 rearrangements. Hybridization analyses with probes for the alpha and beta genes of the T-cell receptor and the T-cell-specific T gamma gene revealed that HPB-MLT cells appear to express approximately equivalent amounts of RNA corresponding to each of the rearranged Ti alpha and Ti beta genes. However, they express a much lower level of T gamma RNA.
An Optimal Iterative Learning Control for Continuous -Time Systems (2006)

A novel iterative learning control method is obtained in this paper using the optimal control theory. The method can control the iterative systems, which have arbitrary initial conditions and also include the disturbance inputs, so that by increasing the iterations encloses the system output to a desired output trajectory and minimizes a quadratic cost function. Physical interpretation of the cost function is that the output of system should approach to the desired output trajectory without many changes in its input. The effectiveness of the presented optimal learning method is illustrated by simulation example