gebhart/patrepeval huggingface dataset:
Erratum: "Evaluating the Potential Usefulness of New Prognostic and Predictive Indicators in Node-Negative Breast Cancer Patients," (1993)

“Evaluating the Potential Usefulness of New Prognostic and Predictive Indicators in Node-Negative Breast Cancer Patients,” by G. Gasparini, F. Pozza, and A. L. Harris J Natl Cancer Inst 85:1206–1219, 1993 (Issue 15). Lines 22–25 of Table 4, column four, (page 1212) should read as follows: “To verify if the study arm treated with adjuvant therapy on the basis of the new indicator obtains a significant improvement in relapse-free survival and&amp;sol;or overall survival.” The Journal regrets the error.
Genetically resistant mice lacking interleukin‐12 are susceptible to infection with Leishmania major and mount a polarized Th2 cell response (1996)

Mice with homologous disruption of the gene coding for either the p35 subunit or the p40 subunit of interleukin-12 (IL-12) and derived from a strain genetically resistant to infection with Leishmania major have been used to study further the role of this cytokine in resistance to infection and the differentiation of functional CD4+ T cell subsets in vivo. Wild-type 129/Sv/Ev mice are resistant to infection with L. major showing only small lesions which resolve spontaneously within a few weeks and develop a type 1 CD4+ T cell response. In contrast, mice lacking bioactive IL-12 (IL-12p35-/- and IL-12p40-/-) developed large, progressing lesions. Whereas resistant mice were able to mount a delayed-type hypersensitivity (DTH) response to Leishmania antigen, susceptible BALB/c mice as well as IL-12-deficient 129/Sv/Ev mice did not show any DTH reaction. To characterize the functional phenotype of CD4+ T cells triggered in infected wild-type mice and IL-12-deficient mice, the expression of mRNA for interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) in purified CD4+ lymph node cells was analyzed. Wild-type 129/Sv/Ev mice showed high levels of mRNA for IFN-gamma and low levels of mRNA for IL-4 which is indicative of a Th1 response. In contrast, IL-12- deficient mice and susceptible BALB/c mice developed a strong Th2 response with high levels of IL-4 mRNA and low levels of IFN-gamma mRNA in CD4+ T cells. Similarly, lymph node cells from infected wild-type 129 mice produced predominantly IFN-gamma in response to stimulation with Leishmania antigen in vitro whereas lymph node cells from IL-12-deficient mice and susceptible BALB/c mice produced preferentially IL-4. Taken together, these results confirm in vivo the importance of IL-12 in induction of Th1 responses and protective immunity against L. major.
Immunoengineering of the Vascular Endothelium to Silence MHC Expression During Normothermic Ex Vivo Lung Perfusion (2018)

Disparities at the major histocompatibility complex (MHC) antigens and associated minor antigens trigger harmful immune responses, leading to graft rejection after transplantation. We showed that MHC-silenced cells and tissues are efficiently protected against rejection. In complex vascularized organs, the endothelium is the major interface between donor and recipient. This study therefore aimed to reduce the immunogenicity of the lung by silencing MHC expression on the endothelium. In porcine lungs, short-hairpin RNAs targeting beta-2-microglobulin and class II-transactivator transcripts were delivered by lentiviral vectors during normothermic ex vivo perfusion to silence swine leukocyte antigen (SLA) I and II expression permanently. The results demonstrated the feasibility of genetically engineering all lung regions, achieving a targeted silencing effect for SLA I and II of 67% and 52%, respectively, without affecting cell viability or tissue integrity. This decrease in immunogenicity carries the potential to generate immunologically invisible organs to counteract the burden of rejection and immunosuppression.
A Burning Question (2005)

There is growing support for the hypothesis that obesity is an inflammatory condition leading to chronic activation of the innate immune system, which ultimately causes progressive impairment of glucose tolerance. Experimental studies in animals and evidence from prospective and longitudinal studies in humans are consistent with an etiologic role of subclinical inflammation in the pathogenesis of type 2 diabetes, primarily as a mediator of obesity-induced insulin resistance. However, the exact chain of molecular events linking overnutrition, activation of the innate immune system, and impairment of insulin signaling in peripheral tissues remains incompletely understood. Notwithstanding this limitation, treating the underlying subclinical inflammation may constitute a novel approach to prevention and/or treatment of type 2 diabetes.
Complement and glomerular disease: new insights (2011)

C5 inhibition appears to be effective therapy for aHUS. An important unresolved question is the role of C5 inhibition in C3 glomerulopathies.
In vivo visualization of myelin water in brain by magnetic resonance (1994)

We exploit the intrinsic difference in magnetic resonance spin-spin relaxation time, T2, between water associated with myelin sheaths and water in other central nervous system tissue in order to measure myelin water content within any region of an image or to generate indirectly a myelin map of the brain. In normal volunteers, myelin water maps give the expected myelin distribution. In multiple sclerosis patients, lesions exhibit different myelin water contents providing insight into the demyelination process unavailable from conventional magnetic resonance images. In vivo myelin measurement has important applications in the clinical management of multiple sclerosis and other white matter diseases.
Charge transfer sensing (1999)

While the transference of charge is an essential aspect of every capacitance sensor, a relatively new form of sensor makes overt use of the principle of charge conservation first deduced by Watson in the 1740s. Updated to use a microcontroller, mosfet switches, fet‐input opamps and band gap references, the principle of charge transference can be used to create an extremely sensitive and stable device with unique properties that transcend those of more pedestrian capacitance sensors. Also known as “QT” sensors, charge transfer sensors can have a dynamic range spanning many decades with noise floors in the sub‐femtofarad regime, allowing differential resolutions of mere fractions of a femtofarad. Such sensors are proving to have unique applications considered heretofore impossible, while also proving themselves as replacements for much more expensive sensing systems using photoelectric, acoustic, RF, and optical imaging techniques.
Cholesterol and Hydroxycholesterol Sulfotransferases: Identification, Distinction from Dehydroepiandrosterone Sulfotransferase, and Differential Tissue Expression (2001)

In humans, the biotransformation of cholesterol and its hydroxylated metabolites (oxysterols) by sulfonation is a fundamental process of great importance. Nevertheless, the sulfotransferase enzyme(s) that carries out this function has never been clearly identified. Cholesterol is a relatively poor substrate for the previously cloned hydroxysteroid sulfotransferase (HST), i.e. dehydroepiandrosterone (DHEA) sulfotransferase (HST1). Recently, cloning of a single human gene that encodes for two proteins related to HST1 was reported. These newly cloned sulfotransferases (HST2a and HST2b), while exhibiting sequence similarity to other members of the soluble sulfotransferase superfamily, also contain unique structural features. This latter aspect prompted an examination of their substrate specificity for comparison with HST1. Thus, HST1, HST2a, and HST2b were overexpressed as fusion proteins and purified. Furthermore, a novel procedure for the isolation of cholesterol and oxysterol sulfonates was developed that was used in association with HPLC to resolve specific sterol sulfonates. HST1 preferentially sulfonated DHEA and, to a lesser extent, oxysterols; whereas cholesterol was a negligible substrate. The reverse, however, was the case for the HST2 isoforms, particularly HST2b, which preferentially sulfonated cholesterol and oxysterols, in contrast to DHEA, which served as a poor substrate for this enzyme. RT-PCR analysis revealed distinct patterns of HST1, HST2a, and HST2b expression. It was particularly notable that both HST2 isoforms, but not HST1, were expressed in skin, a tissue where cholesterol sulfonation plays an important role in normal development of the skin barrier. In conclusion, substrate specificity and tissue distribution studies strongly suggest that HST2a and HST2b, in contrast to HST1, represent normal human cholesterol and oxysterol sulfotransferases. Furthermore, this study represents the first example of the sulfonation of oxysterols by a specific human HST.
Cardiac allograft vasculopathy: advances in understanding its pathophysiology, prevention, and treatment (2004)

These advances have provided hope that allograft vasculopathy may finally be manageable.
Histone Deacetylase Inhibitors: Advancing Therapeutic Strategies in Hematological and Solid Malignancies (2010)

Advancement in the understanding of cancer development in recent years has identified epigenetic abnormalities as a common factor in both tumorigenesis and refractory disease. One such event is the dysregulation of histone deacetylases (HDACs) in both hematological and solid tumors, and has consequently resulted in the development of HDAC inhibitors (HDACI) to overcome this. HDACI exhibit pleiotropic biological effects including inhibition of angiogenesis and the induction of autophagy and apoptosis. Although HDACI exhibit modest results as single agents in preclinical and clinical data, they often fall short, and therefore HDACI are most promising in combinational strategies with either standard treatments or with other experimental chemotherapies and targeted therapies. This review will discuss the induction of autophagy and apoptosis and the inhibition of angiogenesis by HDACI, and also pre-clinical and clinical combination strategies using these agents.
Prolonged CD4 depletion after sequential autologous peripheral blood progenitor cell infusions in children and young adults (2000)

Administration of mobilized peripheral blood progenitor cells (PBPCs) after high-dose chemotherapy rapidly restores multilineage hematopoiesis, but the ability of such products to restore lymphocyte populations remains unclear. In this report, we evaluated immune reconstitution in a series of patients treated with sequential cycles of high-dose chemotherapy, followed by autologous PBPC infusions (median CD34(+) cell dose 7.2 x 10(6) cells/kg [range 2-29.3]). Although patients experienced rapid reconstitution of B cells and CD8(+) T cells, we observed CD4 depletion and diminished immune responsiveness in all patients for several months after completion of therapy. Mature CD4(+) T cells contained within the grafts did not appear to contribute substantially to immune reconstitution because CD4 counts did not differ between recipients of unmanipulated T-cell replete infusions versus CD34 selected, T-cell-depleted infusions. Rather, at 12 months after therapy, total CD4 count was inversely proportional to age (rho = -0.78, P =.04), but showed no relationship to CD34 cell dose (rho = -0.42, P =.26), suggesting that age-related changes within the host are largely responsible for the limited immune reconstitution observed. These results demonstrate that in the autologous setting, the infusion of large numbers of PBPCs is not sufficient to restore T-cell immune competence and emphasize that specific approaches to enhance immune reconstitution are necessary if immune-based therapy is to be used to eradicate minimal residual disease after autologous PBPC transplantation. (Blood. 2000;96:754-762)
A Rationale for Delivery of Osteoinductive Proteins (1996)

Highly pure, recombinant human osteoinductive proteins make it possible to consider programmable osteoneogenesis. Until recently, it was believed that a bioresorbable excipient or physiologic solution would suffice to transport osteoinductive agents from source to wound. After considering surgical requirements, particular bone wound circumstances, scarcity of collateral circulation, phenotype plasticity of mesenchymal progenitor cells, and the morphogens' pleiotrophic effects, it becomes clear that the issue of controlled, programmable osteoneogenesis is a more complicated proposition than can be addressed solely by application of osteoinductive protein. The essential characteristics of a manufactured bone graft substitute (BGS) device are dictated by demands placed on such a device by the surgeons who will employ them and the cells that will occupy them. This review outlines a design process for BGS devices that (1) begins by surveying BGS requirements gathered from the literature from 1991 to 1995, (2) briefly reviews recent in vitro studies of rhBMP-2 and OP- 1, (3) describes commonly encountered circumstances of recipient wound beds, (4) describes behaviors of mesenchymal cells involved in connective tissue repair and regeneration, and (5) concludes with a rationale for design of an osteoinductive bone graft substitute. Emerging from this process is a composite device consisting of a bioresorbable structural polymer, a filamentous velour of hyaluronan (HY), and an osteoinductive protein. The structural polymer, D,D-L,L-polylactic acid, fabricated in the architecture of cancellous bone, is capable of maintaining its structural and architectural properties after being thoroughly saturated with water. Within its interstices is located a filamentous velour of hyaluronan which, when fully hydrated, becomes a viscoelastic gel. It is anticipated that the osteoinductive protein will either be carried on the dried hyaluronic acid velour or in solution via the viscoelastic HY gel.
Morphology and Mechanical Properties of Foamed Polyethylene Blends (2003)

Blends of polyethylene were foamed (593–782 kg/m 3 ) by compression molding. Their morphology was investigated to understand the effect of polymer molecular structure. It was found that the cell diameter distribution can be approximated by a truncated normal distribution. Torsion, flexural and tensile properties were also measured at different strain rates. It was found that the shear, flexural and Young's moduli of blends and their foams increase with increasing strain rate, while their normalized moduli are almost unchanged. We also confirm that thin skins have a definite effect on shear and flexural moduli, but are negligible on tensile moduli. Finally, normalized yield strength and strain are almost independent on strain rate while break strain and toughness increase with increasing molecular weight and decreasing strain rate.
Structure of ITQ-4, a New Pure Silica Polymorph Containing Large Pores and a Large Void Volume (1997)

The new pure silica polymorph ITQ-4, structure code IFR, Si32O64, monoclinic I2/m a = 18.65243(13), b = 13.49597(8), c = 7.63109(6) Å, β = 101.9781(5)°, is a zeolitic material containing a large sinusoidal channel with 12-member ring windows as minimum apertures. Its void volume (0.21 cm3/g) is surpassed only by that of pure silica Beta among the known pure silica polymorphs. The success of the ab initio structure solution from synchrotron powder diffraction data was greatly assisted by the absence of Al and Si−OH defect groups, which generates a very high degree of crystallographic order.
Autophagy contributes to therapy-induced degradation of the PML/RARA oncoprotein (2010)

Treatment of acute promyelocytic leukemia (APL) with all-trans retinoic acid and/or arsenic trioxide represents a paradigm in targeted cancer therapy because these drugs cause clinical remission by affecting the stability of the fusion oncoprotein promyelocytic leukemia (PML)/retinoic acid receptor alpha (RARA). The authors of previous studies have implicated the ubiquitin-proteasome pathway as the main mechanism involved in therapy-induced PML/RARA degradation. Here we have investigated a role of autophagy, a protein degradation pathway that involves proteolysis of intracellular material within lysosomes. We found that both all-trans retinoic acid and arsenic trioxide induce autophagy via the mammalian target of rapamycin pathway in APL cells and that autophagic degradation contributes significantly both to the basal turnover as well as the therapy-induced proteolysis of PML/RARA. In addition, we observed a correlation between autophagy and therapy-induced differentiation of APL cells. Given the central role of the PML/RARA oncoprotein in APL pathogenesis, this study highlights an important role of autophagy in the development and treatment of this disease.
Anatomical, Physiological, and Theoretical Basis for the Antiepileptic Effect of Vagus Nerve Stimulation (1990)

The vagus is a mixed nerve carrying somatic and visceral afferents and efferents. The majority of vagal nerve fibers are visceral afferents and have a wide distribution throughout the central nervous system (CNS) either monosynaptically or via the nucleus of the solitary tract. Besides activation of well-defined reflexes, vagal stimulation produces evoked potentials recorded from the cerebral cortex, the hippocampus, the thalamus, and the cerebellum. Activation of vagal afferents can depress monosynaptic reflexes, decrease the activity of spinothalamic neurons, and increase pain threshold. Depending on the stimulation parameters, vagal afferent stimulation in experimental animals can produce electroencephalographic (EEG) synchronization or desynchronization and has been shown to affect sleep states. The desychronization of the EEG appears to depend on activation of afferent fibers that have conduction velocities of less than or equal to 15 m/s. Vagal afferent stimulation can also influence the activity of interictal cortical spikes produced by topical strychnine application, and either attenuate or stop seizures produced by pentylenetetrazol, 3-mercaptoproprionic acid, maximal electroshock, and topical alumina gel. The mechanisms for the antiepileptic effects of vagal stimulation are not fully understood but probably relate to effects on the reticular activating system. The vagus provides an easily accessible, peripheral route to modulate CNS function.
A 0.2-pm contact filling by 450°C-hydrazine-reduced TiN film with low resistivity (1992)

A commercial single-wafer LPCVD reactor was used in these experiments. The methylhydrazine [(CH3)HNNH2: MH, m.p.= -80°C, b.p.= 87C, vapor pressure= 49.6 TOIT/ 25C] was used as a reduction gas. Wafer was heated from back-side using infrared heater at temperature from 400 to 500OC. Contact resistance was measured using the Kelvin method and the junction leakage current of Si (n+)/Si @-) diode was measured. Sputter Ti film of 300A was used as a contact metal to Si. The deposition rate of h4H-reduced TiN showed a mass transport-limited reaction, increasing with the MH flow rate, and was several order of magnitude higher than that of 3-reduction (Fig. 1). The high reactivity of MH chemistry agreed with our previous study [2]. The film deposited at 400°C showed a typical 6 phase of TiN structure (Fig. 2). The resistivity decreased as the deposition temperature increased, approaching to 90 pWm at 500°C (Fig. 3). This value was lower than that of MOCVD [3] and was obtained by 3-reduction above 70O0C, as shown in Figure 3. The C1 concentration in TiN film decreased as deposition temperature increased, with a tendency similar to the film resistivity (Fig. 4). The MH-reduced TiN film deposited at 450°C did not generate the A1 corrosion even after exposing to moisture for 168 hours due to the low C1 concentration while the NH3-reduced TiN film generated it (Fig. 5). The A1 corrosion was caused by residual C1 above 3 x 1021 atoms/cm3 in TiN film, as shown by hatched region in Figure 4. The thickness ratio at the bottom to the top was above 70% for the deposition for 0.4 pm contact hole (Fig. 6-a). Even 0.2 pm contact hole was completely filled with TiN film (Fig. 6-b). This suggests that the TiN film can be used for giga-bit interconnects alternated to blanket-W contact filling. The contact resistance for Si (n+) and Si (p+) using blanket-W/MH-reduced TiN electrode was similar to that of the reference (blanket-WPVD-TiN) (Fig. 7). The specific contact resistance for Si (n+) and Si (p+) was 1.9 x 10-7 Q.cm2 and 6.9 x 10-7 Q.cm2, respectively. The junction leakage current for both the experiment and reference was in the order of lo- A at 5 V (Fig. 8). Thus, MHreduced TiN film did not damage Si contact and acted as a barrier layer for chemical etching during blanket-W deposition. We have succeeded in filling the 0.2 pm-contact by TiN using MH-reduction of Tick. The Tick-MH reaction proves the capability of low-temperature, low-resistivity, and no-damage contact metallization. The 0.2 pm contact filling opens the way the multilevel-interconnection for giga-bit devices.
Rapid and simple method for purification of nucleic acids (1990)

We have developed a simple, rapid, and reliable protocol for the small-scale purification of DNA and RNA from, e.g., human serum and urine. The method is based on the lysing and nuclease-inactivating properties of the chaotropic agent guanidinium thiocyanate together with the nucleic acid-binding properties of silica particles or diatoms in the presence of this agent. By using size-fractionated silica particles, nucleic acids (covalently closed circular, relaxed circular, and linear double-stranded DNA; single-stranded DNA; and rRNA) could be purified from 12 different specimens in less than 1 h and were recovered in the initial reaction vessel. Purified DNA (although significantly sheared) was a good substrate for restriction endonucleases and DNA ligase and was recovered with high yields (usually over 50%) from the picogram to the microgram level. Copurified rRNA was recovered almost undegraded. Substituting size-fractionated silica particles for diatoms (the fossilized cell walls of unicellular algae) allowed for the purification of microgram amounts of genomic DNA, plasmid DNA, and rRNA from cell-rich sources, as exemplified for pathogenic gram-negative bacteria. In this paper, we show representative experiments illustrating some characteristics of the procedure which may have wide application in clinical microbiology.
Impact of Transgenic VIP3A × Cry1Ab Lepidopteran-resistant Field Corn on the Nontarget Arthropod Community (2005)

Abstract A field experiment was conducted over 3 yr to assess the effects of transgenic field corn expressing stacked lepidopteran-active Bacillus thuringiensis (Bt)-derived VIP3A and Cry1Ab proteins on nontarget arthropods. Effects were compared with an isogenic conventional corn hybrid treated with a foliar insecticide and an isogenic control without insecticides. Plant inspections, pitfall traps, sticky cards, and emergence traps determined the abundance and diversity of plant, aerial, and surface-dwelling communities. More than 500,000 arthropods were enumerated, representing 203 taxonomic groups in 112 families and 13 orders. In terms of abundance, 70% of the arthropods were saprovores, 13% were herbivorous insects, 14% were predators, and 3% were parasitoids. Overall biodiversity and community-level responses were not significantly affected by expression of the stacked VIP3A and Cry1Ab proteins. Densities of most nontarget taxa exposed to the Bt hybrid showed no differences compared with the isogenic control. However, significant changes in certain taxa did occur in the Bt plots, which were indirectly related to plant-mediated factors, prey density responses, and the absence of plant injury. Arthropod communities in the insecticide-treated plots displayed both negative and positive changes in the abundances of individual taxa. Together, effects observed in the Bt plots were significantly less than the community disturbances caused by insecticide applications. Changes in nontarget communities in plots previously exposed to insecticides and the Bt hybrid did not carryover to the following growing season. Major arthropods as bioindicators, routes of exposures, and food web interactions relative to the observed effects are discussed.