gebhart/patrepeval huggingface dataset:
An Eosinophil-Dependent Mechanism for the Antitumor Effect of Interleukin-4 (1992)

Murine interleukin-4 (IL-4) exhibits potent antitumor activity when present at the site of tumor cell challenge. Associated with tumor cell death is the appearance of an inflammatory infiltrate comprised predominantly of eosinophils and macrophages, but with few lymphocytes. Antibodies that specifically block the accumulation of granulocytes at the site of inflammation were injected in vivo to define the cell type responsible for the antitumor action of IL-4. These studies implicate eosinophils in IL-4-mediated tumor cytotoxicity. The lymphoid-independent nature of IL-4 action is supported by the analysis of mutant mouse strains with defined lymphocyte immunodeficiencies. The observed regression of established tumor masses by localized IL-4 action provides a rationale for exploring IL-4-mediated tumor killing as a potential therapy for human malignant disorders.
Propofol binding to human blood proteins. (1995)

The binding of the intravenous anesthetic propofol (CAS 2078-54-8) to human native plasma, hemoglobin and serum albumin was studied by means of equilibrium dialysis. Propofol binding to plasma over the large concentration range from 0.04 to 150 micrograms/ml was independent on the substrate concentration and amounted 97.4-98.6%. Serum albumin and hemoglobin also showed a marked binding for propofol. A 4% solution of albumin bound 88.7% and hemoglobin 86.2% of the anesthetic. In studies with constant protein concentration and variation of the propofol concentration a decrease of the percentage bound with increasing substrate concentration was seen for hemoglobin, indicating saturable binding sites. The opposite was found for the interaction between propofol and albumin: increase of the binding extent with increasing substrate concentration.
Autoimmune Neuromuscular Disorders (2011)

Autoimmune neuromuscular disorders affecting peripheral nerves, neuromuscular junction or muscle have a wide clinical spectrum with diverse pathogenetic mechanisms. Peripheral nervous system may be targeted in the context of complex immune reactions involving different cytokines, antigen-presenting cells, B cells and different types of T cells. Various immunomodulating and cytotoxic treatments block proliferation or activation of immune cells by different mechanisms attempting to control the response of the immune system and limit target organ injury. Most treatment protocols for autoimmune neuromuscular disorders are based on the use of corticosteroids, intravenous immunoglobulins and plasmapheresis, with cytotoxic agents mostly used as steroid-sparing medications. More recently, development of specific monoclonal antibodies targeting individual cell types allowed a different approach targeting specific immune pathways, but these new treatments are also associated with various adverse effects and their long-term efficacy is still unknown.
Approach toward environmental stabilization of chemical amplification resists. (1993)

A molecular design for stabilization of chemical amplification resists toward airborne contamination is described, which is based on our observation that glass transition temperatures (Tg) primarily govern the absorption of N-methylpyrrolidone (NMP) vapor in thin polymer films. Employing the meta-isomer (T g = 85 C) of poly(t-butoxycarbonyloxystyrene) (PBOCST) to replace the para-isomer (T g =130 C) in the IBM's tBOC resist has proved the validity of our T g theory in NMP uptake measurements as well as in negative lithographic imaging. Furthermore, the use of a meta-isomer to lower T g for better annealing has been shown to be also useful in decreasing NMP absorption in aqueous base developable,, positive copolymer resists, providing f increased contamination resistance.
Favorable Prognostic Impact of NPM1 Mutations in Older Patients With Cytogenetically Normal De Novo Acute Myeloid Leukemia and Associated Gene- and MicroRNA-Expression Signatures: A Cancer and Leukemia Group B Study (2009)

NPM1 mutations have favorable prognostic impact in older patients with CN-AML, especially those age >or= 70 years. The gene- and microRNA-expression profiles suggest that NPM1 mutations constitute a marker defining a biologically homogeneous entity in CN-AML that might be treated with specific and/or targeted therapies across age groups.
Albumin Modified With Mannose 6–Phosphate: A Potential Carrier for Selective Delivery of Antifibrotic Drugs to Rat and Human Hepatic Stellate Cells (1999)

The hallmark of liver fibrosis is an increased extracellular matrix deposition, caused by an activation of hepatic stellate cells (HSC). Therefore, this cell type is an important target for pharmacotherapeutic intervention. Antifibrotic drugs are not efficiently taken up by HSC or may produce unwanted side-effects outside the liver. Cell-specific delivery can provide a solution to these problems, but a specific drug carrier for HSC has not been described until now. The mannose 6-phosphate/insulin-like growth factor II (M6P/IGF-II) receptor, which is expressed in particular upon HSC during fibrosis, may serve as a target-receptor for a potential carrier. The aim of the present study was to examine if human serum albumin (HSA) modified with mannose 6-phosphate (M6P) is taken up by HSC in fibrotic livers. A series of M6Px-modified albumins were synthetized: x = 2, 4, 10, and 28. Organ distribution studies were performed to determine total liver uptake. The hepatic uptake of M6Px-HSA increased with increasing M6P density. M6Px-HSA with a low degree of sugar loading (x = 2-10) remained in the plasma and accumulated for 9% +/- 0.5% or less in fibrotic rat livers. An increase in the molar ratio of M6P:HSA to 28:1 caused an increased liver accumulation to 59% +/- 9% of the administered dose. Furthermore, we determined quantitatively the in vivo intrahepatic distribution of M6Px-HSA using double-immunostaining techniques. An increased substitution of M6P was associated with an increased accumulation in HSC; 70% +/- 11% of the intrahepatic staining for M6P28-HSA was found in HSC. We also demonstrate that M6P-modified bovine serum albumin (BSA) accumulates in slices of normal and cirrhotic human livers. After incubation of this neoglycoprotein with human tissue, the protein is found in nonparenchymal liver cells. Because M6P-modified albumins are taken up by HSC in fibrotic livers, this neoglycoprotein can be applied as a selective drug carrier for HSC. This technology may create new opportunities for the pharmacological intervention of liver fibrosis.
Survival outcomes of early autologous stem cell transplant (ASCT) followed by lenalidomide, bortezomib, and dexamethasone (RVD) maintenance in patients with high-risk multiple myeloma (MM). (2012)

8100 Background: Despite markedly improved survival rates for MM pts in the last decade, 15-20% of pts with high risk genetics continue to have dismal outcomes with a median PFS of 18.5 months (Kapoor P et al). In this subset of pts, efforts are needed to improve response rates and prolong the response duration, but doing so without genotoxic therapy as this has been shown not to improve outcomes (Barlogie et al). Methods: We evaluated 37 pts with high risk features [del17p (n=16), t(4;14) (n=1), t(14;16) (n=4) by FISH/CTG; hypodiploidy (n=9), del 13 (n=16); complex karyotype (n=14) by CTG; PCL (n=7) and atypical presentation (n=4)]. After completing induction therapy, all pts underwent ASCT followed by RVD maintenance. 60 days after ASCT following hematological recovery, pts began maintenance [lenalidomide 10 mg/day (days1–21), bortezomib 1.3 mg/m2 and dexamethasone 40 mg once a week (days 1, 8, 15) every 28 days]. Results: The response rates are summarized in the table. 7/36 pts progressed while on RVD maintenance. The median PFS and OS for pts on RVD maintenance has not been reached. Pts with &lt;VGPR pre-ASCT and with &lt;VGPR on RVD maintenance have median PFS of 28 months and 11 months, respectively. 4 pts with prior h/o DVT received anticoagulation, while all others received ASA for DVT prophylaxis. No thrombotic events were seen. There were no grade 3/4 toxicities or treatment-related mortality. The most common toxicities during maintenance schedule were: PN-40% (G1: 26%; G2:14%); G1 rash-10% and G1 fatigue in 78% pts. Cytopenias were seen in 25% pts and dose reductions were made in 50% pts. There is no report of secondary malignancies. Conclusions: Early ASCT followed by RVD maintenance delivers superior response rates in this high risk segment achieving sCR in 47% and ≥VGPR in 73% pts and prevents early relapses. The median PFS and OS have not been reached. RVD maintenance regimen is well tolerated and promising. [Table: see text]
Hereditary sensory and autonomic neuropathies: types II, III, and IV (2007)

The hereditary sensory and autonomic neuropathies (HSAN) encompass a number of inherited disorders that are associated with sensory dysfunction (depressed reflexes, altered pain and temperature perception) and varying degrees of autonomic dysfunction (gastroesophageal reflux, postural hypotention, excessive sweating). Subsequent to the numerical classification of four distinct forms of HSAN that was proposed by Dyck and Ohta, additional entities continue to be described, so that identification and classification are ongoing. As a group, the HSAN are rare diseases that affect both sexes. HSAN III is almost exclusive to individuals of Eastern European Jewish extraction, with incidence of 1 per 3600 live births. Several hundred cases with HSAN IV have been reported. The worldwide prevalence of HSAN type II is very low. This review focuses on the description of three of the disorders, HSAN II through IV, that are characterized by autosomal recessive inheritance and onset at birth. These three forms of HSAN have been the most intensively studied, especially familial dysautonomia (Riley-Day syndrome or HSAN III), which is often used as a prototype for comparison to the other HSAN. Each HSAN disorder is likely caused by different genetic errors that affect specific aspects of small fiber neurodevelopment, which result in variable phenotypic expression. As genetic tests are routinely used for diagnostic confirmation of HSAN III only, other means of differentiating between the disorders is necessary. Diagnosis is based on the clinical features, the degree of both sensory and autonomic dysfunction, and biochemical evaluations, with pathologic examinations serving to further confirm differences. Treatments for all these disorders are supportive.
Predicting head pose from speech (2018)

Speech animation, the process of animating a human-like model to give the impression it is talking, most commonly relies on the work of skilled animators, or performance capture. These approaches are time consuming, expensive, and lack the ability to scale. This thesis develops algorithms for content driven speech animation; models that learn visual actions from data without semantic labelling, to predict realistic speech animation from recorded audio.&#13;\nWe achieve these goals by _rst forming a multi-modal corpus that represents the style of speech we want to model; speech that is natural, expressive and prosodic. This allows us to train deep recurrent neural networks to predict compelling animation.&#13;\nWe _rst develop methods to predict the rigid head pose of a speaker. Predicting the head pose of a speaker from speech is not wholly deterministic, so our methods provide a large variety of plausible head pose trajectories from a single utterance. We then apply our methods to learn how to predict the head pose of the listener while in conversation, using only the voice of the speaker. Finally, we show how to predict the lip sync, facial expression, and rigid head pose of the speaker, simultaneously, solely from speech&#13;\n
Dynamic Supply Noise Measurement with All Digital Gated Oscillator for Evaluating Decoupling Capacitance Effect (2007)

This paper proposes an all digital measurement circuit called "gated oscillator" for capturing waveforms of dynamic power supply noise. The gated oscillator is constructed with standard cells, and thus easily embedded in SoCs. The performance of the gated oscillator is testified with fabricated test chips in a 90 nm process. Characteristics of decoupling capacitance are discussed focusing on channel length and distance, based on supply noise waveforms measured by the gated oscillator.
The Volatile Oil Composition of Fresh and Air-Dried Buds of Cannabis sativa (1996)

The composition of the steam-distilled volatile oil of fresh and air-dried, indoor-grown marijuana was studied by GC/FID and GC/MS. In all, 68 components were detected of which 57 were fully identified. Drying of the plant material had no effect on the qualitative composition of the oil and did not affect the ability of individuals familiar with marijuana smell to recognize the odor.
Glioma Immunology and Immunotherapy (2000)

Modern molecular biology and immunology techniques have yielded a wealth of new data about glioma immunobiology. Armed with this information, many investigators have proposed novel means to stimulate antiglioma immune responses. Although definitive clinical results remain to be seen, the current renaissance in glioma immunology and immunotherapy shows great promise for the future.
Mechanism by Which Mutations at His274 Alter Sensitivity of Influenza A Virus N1 Neuraminidase to Oseltamivir Carboxylate and Zanamivir (2002)

Oseltamivir carboxylate is a potent and specific inhibitor of influenza neuraminidase (NA). An influenza A/H1N1 variant selected in vitro with reduced susceptibility to oseltamivir carboxylate contains a His274Tyr mutation. To understand the mechanism by which a His274Tyr mutation gives rise to drug resistance, we studied a series of NA variant proteins containing various substitutions at position 274. Replacement of His274 with larger side chain residues (Tyr or Phe) reduced the NA sensitivity to oseltamivir carboxylate. In contrast, replacement of His274 with smaller side chain residues (Gly, Asn, Ser, and Gln) resulted in enhanced or unchanged sensitivity to oseltamivir carboxylate. Previous studies have suggested that the slow-binding inhibition of NA by oseltamivir carboxylate is a result of the reorientation of Glu276. Loss of this slow-binding inhibition in the His274Tyr and His274Phe mutant NA but not in His274Asn, His274Gly, His274Ser, or His274Gln supports the conclusion that the conformational change of Glu276 is restricted in the His274Tyr and His274Phe mutant NA upon oseltamivir carboxylate binding. Interestingly, His274Asn, as well as His274Gly, His274Ser, and His274Gln, also displayed reduced sensitivity to zanamivir and its analogue, 4-amino-Neu5Ac2en. Substitution of His274 with Tyr in influenza A/Tokyo/3/67 (H3N2) recombinant NA did not affect the susceptibility to oseltamivir carboxylate. These data indicate that the volume occupied by the amino acid side chain at position 274 can influence the sensitivities of influenza N1 NA but not of N2 NA to both oseltamivir carboxylate and zanamivir.
A mutant T7 phage promoter is specifically transcribed by T7‐RNA polymerase in mammalian cells (1993)

The phage T7 promoter/polymerase system is highly specific in bacteria in contrast to that observed in mammalian cells. A number of cell lines exhibit a considerable level of expression from the T7 promoter, even in the absence of T7-RNA polymerase. Here, we demonstrate that nuclear-factor-including components of the TFIID fraction, bind to the T7 promoter and inhibit transcription by T7-RNA polymerase. In order to increase the specificity of the promoter for T7-RNA polymerase and to abolish binding of nuclear factors, a novel strategy for the selection of randomly mutated promoters was established. The strategy involves adsorption of mutant promoters to HeLa extracts and binding of the free oligonucleotides to T7-RNA polymerase, cloning, and functional testing of the recombinants. After selection, the resulting mutant promoters showed an increase in specificity for transcription by T7-RNA polymerase.
Phase 2 study of sodium phenylbutyrate in ALS (2008)

The objective of the study was to establish the safety and pharmacodynamics of escalating dosages of sodium phenylbutyrate (NaPB) in participants with ALS. Transcription dysregulation may play a role in the pathogenesis of ALS. Sodium phenylbutyrate, a histone deacetylase inhibitor, improves transcription and post-transcriptional pathways, promoting cell survival in a mouse model of motor neuron disease. Forty research participants at eight sites enrolled in an open-label study. Study medication was increased from 9 to 21 g/day. The primary outcome measure was tolerability. Secondary outcome measures included adverse events, blood histone acetylation levels, and NaPB blood levels at each dosage. Twenty-six participants completed the 20-week treatment phase. NaPB was safe and tolerable. No study deaths or clinically relevant laboratory changes occurred with NaPB treatment. Histone acetylation was decreased by approximately 50% in blood buffy-coat specimens at screening and was significantly increased after NaPB administration. Blood levels of NaPB and the primary metabolite, phenylacetate, increased with dosage. While the majority of subjects tolerated higher dosages of NaPB, the lowest dose (9 g/day), was therapeutically efficient in improving histone acetylation levels.
An Extended Kalman Filter for Quaternion-Based Attitude Estimation (2000)

Abstract: This paper presents an extended Kalman filter for real-time estimation of rigid body orientation using the newly developed MARG (Magnetic, Angular Rate, and Gravity) sensors. Each MARG sensor contains a three-axis magnetometer, a three-axis angular rate sensor, and a three-axis accelerometer. The filter represents rotations using quaternions rather than Euler angles, which eliminates the long-standing problem of singularities associated with attitude estimation. A process model for rigid body angular motions and angular rate measurements is defined. The process model converts angular rates into quaternion rates, which are integrated to obtain quaternions. The Gauss-Newton iteration algorithm is utilized to find the best quaternion that relates the measured accelerations and earth magnetic field in the body coordinate frame to calculated values in the earth coordinate frame. The best quaternion is used as part of the measurements for the Kalman filter. As a result of this approach, the measurement equations of the Kalman filter become linear, and the computational requirements are significantly reduced, making it possible to estimate orientation in real time. Extensive testing of the filter with synthetic data and actual sensor data proved it to be satisfactory. Test cases included the presence of large initial errors as well as high noise levels. In all cases the filter was able to converge and accurately track rotational motions. 1.
Differential Expression of IGF Components and Insulin Receptor Isoforms in Human Seminoma Versus Normal Testicular Tissue (2005)

Insulin-like growth factors (IGF) have mitogenic and antiapoptotic functions, and may be involved in tumor growth. The purpose of the study was to investigate the role of IGF components in seminoma compared to normal testis. Normal testicular tissues from autopsy cases and seminoma from surgery cases were obtained for microarray and real-time reverse transcription polymerase chain reaction (RT-PCR) analysis of IGF-1, IGF-2, IGF receptor type 1 (IGF-R1), IGF-R2, insulin receptor isoforms A (IR-A) and B (IR-B), and IGF-binding proteins (IGFBP) 1-6. IGF-2 was localized by immunohistochemistry. IGFBP-5 protein expression was evaluated by Western blot analysis. mRNA expression in microarray and real-time RT-PCR showed similar tendencies: IGF-1, IGF-R1, IGF-R2, IR-A, and IGFBP-2 were not different in both groups. IGF-2, IR-B, IGFBP-1, IGFBP-4, and IGFBP-6 mRNA were downregulated in seminoma. IGFBP-3 tended to be upregulated in pT1 seminoma, but downregulated in pT2 stages. IGFBP-5 and IGF-2 protein expression correlated with mRNA expression. In conclusion, downregulation of mainly inhibiting IGFBPs may allow a stimulated tumor growth. The downregulated IGF-2 does not seem to be involved in the growth regulation of seminoma. Constantly expressed genes (e.g., IGF-1, IGF-R1, IR-A, and IGFBP-2) may reflect an involvement in spermatogenesis, but may also play a major role in tumor growth as their expression is not downregulated despite the lack of spermatogenesis in tumor tissue.
A compensator for the effects of high-order polarization mode dispersion in optical fibers (2000)

We present a polarization mode dispersion compensator for the rotation of the principal states with frequency. This compensator requires only two control elements more than existing first-order compensators. These are the position of one polarization controller and the setting of a single delay. With the proposed scheme, compensation for first order can be decoupled from the compensation for higher orders and controlled independently. The effect of the compensator on signal transmission is evaluated with extensive numerical simulations.
Development of Orthotopic Pancreatic Tumor Mouse Models (2012)

Genetically engineered mouse models of pancreatic cancer that recapitulate human pancreatic tumorigenesis have been established. However, the cost associated with generating and housing these mice can be -prohibitive. Tumor latency and progression to invasive diseases in these models are also highly variable. Xenograft mouse models of human pancreatic cancer including heterotopic and orthotopic have been widely used in preclinical studies for their comparatively low cost and rapid, predictable tumor growth. Of the two, orthotopic tumor mouse models are preferred because they offer tissue site-specific pathology, allow studies of metastasis, and are generally deemed more clinically relevant. Here we describe the procedures of implanting cancer cell lines to generate orthotopic mouse models for pancreatic cancer.
End Organ Function With Prolonged Nonpulsatile Circulatory Support (1995)

The hypothesis tested in these studies was that long-term circulatory support with a nonpulsatile device is safe and causes no end organ dysfunction. An inexpensive, small centrifugal pump with a 7 L/min capacity was implanted in 6 sheep (15 acute implants have previously been reported). The inlet cannula was placed in the left atrium and the outlet graft anastomosed to the descending aorta. A percutaneous cable supplied DC power and heparinized saline (10 ml/hr) for lubrication. Outputs of pump flow, stator, animal core temperature, pump power consumption, and RPM were monitored throughout the course of each experiment. The sheep moved freely within a large pen using an overhead swivel/tether system that carried all input and output lines. Four sheep survived longer than 4 weeks, and the indices of end organ function were analyzed at 28 days. No animal revealed any neurologic dysfunction. Hemoglobin was 9.075 +/- 0.78 g/dl at 28 days, as opposed to 7.475 +/- 0.68 (p = 0.002) before surgery. The blood urea nitrogen was 9.250 +/- 4.57 versus 14 +/- 5.72 mg/dl (p = 0.041), creatinine was 0.775 +/- .10 versus 0.775 +/- 0.05 mg/dl (p > or = 0.999), total bilirubin was 0.425 +/- 0.2 versus 0.225 +/- 0.05 mg/dl (p = 0.092), serum glutamic oxaloacetic transaminase was 74.75 +/- 24 versus 106.25 +/- 15.84 IU/L (p = 0.015), serum glutamic pyruvic transaminase was 36 +/- 28.7 versus 28.3 +/- 5.7 IU/L (p = 0.25), and total protein was 6.675 +/- 0.49 versus 5.47 +/- 0.15 g/dl (p = 0.025). It is concluded that these animals adapted very well to pulseless circulatory support. The results of these studies support the concept of an inexpensive, implantable, centrifugal pump as a ventricular assist device.
Somatic Activation of KIT in Distinct Subtypes of Melanoma (2006)

KIT is an important oncogene in melanoma. Because the majority of the KIT mutations we found in melanoma also occur in imatinib-responsive cancers of other types, imatinib may offer an immediate therapeutic benefit for a significant proportion of the global melanoma burden.