gebhart/patrepeval huggingface dataset:
Complement Depletion Facilitates the Infection of Multiple Brain Tumors by an Intravascular, Replication-Conditional Herpes Simplex Virus Mutant (2000)

Intravascular routes of administration can provide a means to target gene- and virus-based therapies to multiple tumor foci located within an organ, such as the brain. However, we demonstrate here that rodent plasma inhibits cell transduction by replication-conditional (oncolytic) herpes simplex viruses (HSV), replication-defective HSV, and adenovirus vectors. In vitro depletion of complement with mild heat treatment or in vivo depletion by treatment of athymic rats with cobra venom factor (CVF) partially reverses this effect. Without CVF, inhibition of cell infection by HSV is observed at plasma dilution as high as 1:32, while plasma from CVF-treated animals displays anti-HSV activity at lower dilutions (1:8). When applied to the therapy of intracerebral brain tumors, in vivo complement depletion facilitates the initial infection (assayed at the 2-day time point) by an intra-arterial replication-conditional HSV of tumor cells, located within three separate and distinct human glioma masses. However, at the 4-day time point, no propagation of HSV from initially infected tumor cells could be observed. Previously, we have shown that the immunosuppressive agent, cyclophosphamide (CPA), facilitates the in vivo propagation of an oncolytic HSV, delivered intravascularly, within infected multiple intracerebral masses, by inhibition of both innate and elicited anti-HSV neutralizing antibody response (K. Ikeda et al., Nat. Med. 5:881-889, 1999). In this study, we thus show that the addition of CPA to the CVF treatment results in a significant increase in viral propagation within infected tumors, measured at the 4-day time period. The concerted action of CVF and CPA significantly increases the life span of athymic rodents harboring three separate and large glioma xenografts after treatment with intravascular, oncolytic HSV. Southern analysis of viral genomes analyzed by PCR reveals the presence of the oncolytic virus in the brains, livers, spleens, kidneys, and intestine of treated animals, although none of these tissues displays evidence of HSV-mediated gene expression. In light of clinical trials of oncolytic HSV for malignant brain tumors, these findings suggest that antitumor efficacy may be limited by the host innate and elicited humoral responses.
Clinical and hematologic findings in canine ehrlichiosis (1985)

The clinical and hematologic findings for 56 dogs with ehrlichiosis were studied retrospectively. All dogs had a high serum antibody titer to Ehrlichia canis. The frequency of bleeding disorders, thrombocytopenia, and pancytopenia in these dogs was lower than previously described for dogs so affected. A bleeding disorder caused by a suspected qualitative platelet defect was found in some dogs that did not have thrombocytopenia. Megakaryocytic hyperplasia and high numbers of plasma cells were observed frequently on marrow aspirate smears. The clinical and laboratory findings of dogs were variable and were considered nonspecific for ehrlichiosis.
Cumulative Incidence of Childhood-Onset IDDM is Unaffected by Pertussis Immunization (1997)

The comparison of the cumulative incidence of IDDM, up to the age of 12 years, in birth cohorts with high and low exposure to pertussis vaccine does not support the hypothesis that pertussis could induce autoimmunity to the beta-cell that may lead to IDDM.
Incidence of childhood type 1 diabetes worldwide. Diabetes Mondiale (DiaMond) Project Group. (2000)

The range of global variation in the incidence of childhood type 1 diabetes is even larger than previously described. The earlier reported polar-equatorial gradient in the incidence does not seem to be as strong as previously assumed, but the variation seems to follow ethnic and racial distribution in the world population.
Mast Cell-Derived Histamine Mediates Cystitis Pain (2008)

These data demonstrate that mast cells promote cystitis pain and bladder pathophysiology through the separable actions of histamine and TNF, respectively. Therefore, pain is independent of pathology and inflammation, and histamine receptors represent direct therapeutic targets for pain in IC and other chronic pain conditions.
Estimation of language models for new spoken language applications (2002)

Spoken language interfaces can provide natural communication for many database retrieval tasks. The CMU ATIS system provides an example of accessing airline information using spoken natural language queries. However, a lot of training data is needed to develop a spoken language application. For example, one needs training data to generate a language model that can be used by the recognizer to reduce the search space. The author addresses some issues arising from small amount of training data available for a new spoken language application. The author is working on a spoken language interface to access information from a library catalogue. The catalogue contains around 13,000 titles, 6000 authors and 19000 subjects. There an more than 20,000 words in the dictionary. The user can seek information about books, authors, subjects, publishers, etc. For example, I'd like to see books dealing with Science fiction by Clarke. The author describes some language modelling experiments for this task. The author briefly describes a speech interface for a library catalogue. The author also reviews class-based language models and describes their limitations. Finally, the author presents the approach to building statistical language models for new spoken language applications. This is important because a lot of training data is normally needed to generate a language model. However, it is not practical to have or collect a large corpus of data for each new spoken language application.
Synthesis of β-cyclodextrin conjugated superparamagnetic iron oxide nanoparticles for selective binding and detection of cholesterol crystals (2012)

Water-soluble, β-cyclodextrin conjugated superparamagnetic nanoparticles have been constructed. These particles showed selective binding to cholesterol crystals, which opens the door for the detection of cholesterol crystal-related diseases such as atherosclerosis by magnetic resonance imaging (MRI).
Noise study of low-dimensional quantum-well semiconductor laser amplifiers (1992)

Low noise characteristics of semiconductor laser amplifiers (SLAs) consisting of low-dimensional quantum-well structures are obtained theoretically using density matrix theory. Due to a sharper gain spectrum as well as a smaller population inversion parameter in quantum-wire and quantum-box structures, predominant two beat noises of traveling-wave SLAs were found to be reduced in the lower dimensional quantum-well structures, even in solitary devices without a narrow bandpass filter. The noise figure can be reduced to 3.3 dB in a quantum-box structure, which nears the theoretical limit of 3 dB.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Angiopoietin-Like 7 Is an Anti-Angiogenic Protein Required to Prevent Vascularization of the Cornea (2015)

ANGPTL7, which is abundantly expressed in keratocytes, plays a major role in maintaining corneal avascularity and transparency.
Cetuximab in combination with oxaliplatin/5-fluorouracil (5-FU)/folinic acid (FA) (FOLFOX-4) in the first-line treatment of patients with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer: An international phase II study (2005)

3535 Background: Cetuximab (Erbitux), an IgG1 monoclonal antibody that specifically targets EGFR the receptor, is effective in combination with irinotecan or irinotecan/5-FU/FA in patients with EGFR-expressing mCRC in the first and second-/subsequent-line settings. The study was designed to evaluate the safety and efficacy of cetuximab in combination with FOLFOX-4 as first-line treatment. Methods: Pts with non-resectable EGFR-expressing mCRC, with no prior chemotherapy, were treated with cetuximab (400 mg/m2 week 1 and 250 mg/m2 weekly thereafter) plus FOLFOX-4 (every 2 weeks: oxaliplatin 85 mg/m2, day 1; FA 200 mg/m2 IV 2h and 5-FU 400 mg/m2 IV bolus followed by 600 mg/m2 IV for 22h, days 1 and 2) until progressive disease (PD) or unacceptable toxicity. Preliminary Results: Of the 62 pts, median ECOG performance status 0 (0–2), screened, 52 pts (84%) had EGFR-expressing metastatic disease, 43 pts, median age 65 yrs (range 43–78) were finally enrolled. All of the patients are assessable for safety and efficacy. Main adverse events grade 3/4 (pts ≥10%, multiple cycle) observed per pt: acne-like rash 30.2%, diarrhea 25.6%, neurotoxicity 25.6%, neutropenia 20.9%, stomatitis/mucositis 16.3%. The efficacy data on 42 pts yielded an overall confirmed response rate of 72%, comprising 4 (9%) complete responses (CR) and 27 (63%) partial responses (PR). There were also 10 (23%) pts with stable disease to yield a disease control rate of 95%. 8 pts are still on treatment. PFS is 10.2 months. To date, 10 pts have undergone surgery of their metastases: 8 for liver, 1 for lung, 1 for suprarenal gland metastases (9 R0 resections). Conclusions: The combination of cetuximab and FOLFOX-4 has an acceptable safety profile and demonstrates advantages in response rate in the first-line treatment of patients with EGFR-expressing mCRC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck, Merck KGaA Amgen, Baxter, Roche, sanofi-aventis Merck KGaA Bristol-Myers Squibb, Lilly Oncology, Merck, Roche, sanofi-aventis Lilly Oncology, Roche, sanofi-aventis
Leukocyte-Poor Blood (1986)

The conventional techniques used to prepare leukocyte-poor red cell concentrates are described. These techniques conveniently group by their primary processing modalities which are centrifugation, freeze thawing, cell washing, and filtration. Each of these procedures has unique logistical requirements. The complexity, need of dedicated capital equipment, and stringent quality assurance requirements make the use of some of these techniques impractical for the hospital blood bank laboratory. The majority of patients benefit from the receipt of leukocyte-poor blood products prepared by an "in-line" microaggregate filtration technique. Those patients with symptoms which prove to be refractory to microaggregate-filtered blood products and those who require highly purified red cell concentrates to forestall sensitization to transplantation antigens should receive blood prepared either by the cryopreservation/deglycerolization technique or by cotton wool filtration.
Seborrheic dermatitis (2003)

Upon completing this paper, the reader should be aware of the clinical presentation of seborrheic dermatitis and which populations are at particular risk of developing this disorder. In addition, s/he will be aware of the role of Malassezia yeasts in seborrheic dermatitis and the way in which knowledge of the importance of these yeasts has altered the treatment of this disorder.
AGILE: elastic distributed resource scaling for Infrastructure-as-a-Service (2013)

Dynamically adjusting the number of virtual machines (VMs) assigned to a cloud application to keep up with load changes and interference from other uses typically requires detailed application knowledge and an ability to know the future, neither of which are readily available to infrastructure service providers or application owners. The result is that systems need to be over-provisioned (costly), or risk missing their performance Service Level Objectives (SLOs) and have to pay penalties (also costly). AGILE deals with both issues: it uses wavelets to provide a medium-term resource demand prediction with enough lead time to start up new application server instances before performance falls short, and it uses dynamic VM cloning to reduce application startup times. Tests using RUBiS and Google cluster traces show that AGILE can predict varying resource demands over the medium-term with up to 3.42 × better true positive rate and 0.34 × the false positive rate than existing schemes. Given a target SLO violation rate, AGILE can efficiently handle dynamic application workloads, reducing both penalties and user dissatisfaction. 1
Selective Tumor Cell Targeting Using Low-Affinity, Multivalent Interactions (2007)

This report highlights the advantages of low-affinity, multivalent interactions to recognize one cell type over another. Our goal was to devise a strategy to mediate selective killing of tumor cells, which are often distinguished from normal cells by their higher levels of particular cell surface receptors. To test whether multivalent interactions could lead to highly specific cell targeting, we used a chemically synthesized small-molecule ligand composed of two distinct motifs: (1) an Arg-Gly-Asp (RGD) peptidomimetic that binds tightly (Kd approximately 10(-9)M) to alphavbeta3 integrins and (2) the galactosyl-alpha(1-3)galactose (alpha-Gal epitope), which is recognized by human anti-alpha-galactosyl antibodies (anti-Gal). Importantly, anti-Gal binding requires a multivalent presentation of carbohydrate residues; anti-Gal antibodies interact weakly with the monovalent oligosaccharide (Kd approximately 10(-5)M) but bind tightly (Kd approximately 10(-11) M) to multivalent displays of alpha-Gal epitopes. Such a display is generated when the bifunctional conjugate decorates a cell possessing a high level of alphavbeta3 integrin; the resulting cell surface, which presents many alpha-Gal epitopes, can recruit anti-Gal, thereby triggering complement-mediated lysis. Only those cells with high levels of the integrin receptor are killed. In contrast, doxorubicin tethered to the RGD-based ligand affords indiscriminate cell death. These results highlight the advantages of exploiting the type of the multivalent recognition processes used by physiological systems to discriminate between cells. The selectivity of this strategy is superior to traditional, abiotic, high-affinity targeting methods. Our results have implications for the treatment of cancer and other diseases characterized by the presence of deleterious cells.
A Direct Approach to False Discovery Rates (2002)

Summary Multiple-hypothesis testing involves guarding against much more complicated errors than single-hypothesis testing. Whereas we typically control the type I error rate for a single-hypothesis test, a compound error rate is controlled for multiple-hypothesis tests. For example, controlling the false discovery rate FDR traditionally involves intricate sequential p-value rejection methods based on the observed data. Whereas a sequential p-value method fixes the error rate and estimates its corresponding rejection region, we propose the opposite approach—we fix the rejection region and then estimate its corresponding error rate. This new approach offers increased applicability, accuracy and power. We apply the methodology to both the positive false discovery rate pFDR and FDR, and provide evidence for its benefits. It is shown that pFDR is probably the quantity of interest over FDR. Also discussed is the calculation of the q-value, the pFDR analogue of the p-value, which eliminates the need to set the error rate beforehand as is traditionally done. Some simple numerical examples are presented that show that this new approach can yield an increase of over eight times in power compared with the Benjamini–Hochberg FDR method.
The Functional and Regulatory Roles of Sigma Factors in Transcription (1998)

In prokaryotic cells, a single subunit of RNA polymerase, called sigma, orchestrates the process of transcription initiation. Sigma binds to the multisubunit coreRNA polymerase (α2ββ′), creating RNA polymeraseholoenzyme (α2ββ′σ), which performs transcription initiation. Holoenzyme recognizes the two conserved hexamer sequences that constitute a prokaryotic promoter,exposes the single-stranded DNA template necessary fortranscription initiation, and begins synthesizing thenascent RNA chain. When the nascent RNA is five to tennucleotides long, sigma is released, terminating the initiation phase of transcription. Core RNA polymerase thencarries out the elongation and termination phases of transcriptio...
Electrostatic Activation of Hypervalent Organo‐Iodine Compounds: Bis(onio)‐Substituted Aryliodine(III) Salts (1994)

A new class of compounds, for example 2, synthesized from 1 or iodosobenzene, are the title compounds in this article. The oxidation potential of 1 is increased considerably by bis(onio) substitution; thus, these new systems can be used as potent oxidants. Applications include dehydrogenations of monohydrazones to give diazo compounds and of 1,2-bishydrazones to give alkynes.
Accounting for Human Polymorphisms Predicted to Affect Protein Function (2002)

A major interest in human genetics is to determine whether a nonsynonymous single-base nucleotide polymorphism (nsSNP) in a gene affects its protein product and, consequently, impacts the carrier's health. We used the SIFT (Sorting Intolerant From Tolerant) program to predict that 25% of 3084 nsSNPs from dbSNP, a public SNP database, would affect protein function. Some of the nsSNPs predicted to affect function were variants known to be associated with disease. Others were artifacts of SNP discovery. Two reports have indicated that there are thousands of damaging nsSNPs in an individual's human genome; we find the number is likely to be much lower.
Mathematical model of diffusion in the vitreous humour of the eye (1981)

Experimental tracer studies in the eye have revealed a complex pattern of exchange of material in the vitreous humour with the surrounding media. As an initial stage towards unifying some of those findings, a mathematical model has been developed in which a tracer diffuses from vitreous humour into the retina, choroid and sclera with removal occurring in the capillary bed of the choroid. A numerical solution has been obtained which is applicable to a three-dimensional simulation of the post-lenticular tissues of the eye. Good agreement is demonstrated between the predictions of the model and experimental results for xenon.
Detect to Track and Track to Detect (2017)

Recent approaches for high accuracy detection and tracking of object categories in video consist of complex multistage solutions that become more cumbersome each year. In this paper we propose a ConvNet architecture that jointly performs detection and tracking, solving the task in a simple and effective way. Our contributions are threefold: (i) we set up a ConvNet architecture for simultaneous detection and tracking, using a multi-task objective for frame-based object detection and across-frame track regression; (ii) we introduce correlation features that represent object co-occurrences across time to aid the ConvNet during tracking; and (iii) we link the frame level detections based on our across-frame tracklets to produce high accuracy detections at the video level. Our ConvNet architecture for spatiotemporal object detection is evaluated on the large-scale ImageNet VID dataset where it achieves state-of-the-art results. Our approach provides better single model performance than the winning method of the last ImageNet challenge while being conceptually much simpler. Finally, we show that by increasing the temporal stride we can dramatically increase the tracker speed.
Transition‐Metal‐Catalyzed Oxidations, 2. Titanium‐ or Zirconium‐Catalyzed Selective Dehydrogenation of Benzyl Alcohols to Aldehydes and Ketones with tert‐Butyl Hydroperoxide (1990)

Abstract Primary and secondary benzyl alcohols are selectivity converted in high yields into the corresponding aldehydes or ketones using tert ‐butyl hydroperoxide and catalytic amounts of titanium or (better) zirconium alcoholates. Aliphatic hydroxy groups, double bonds (except those in allylic position to hydroxy groups), and phenolic hydroxy groups (except those in ortho position to the benzylic alcohol) are not attacked.
Glutamate Receptor Dysfunction and Schizophrenia (1995)

In this article, we advance a unified hypothesis pertaining to combined dysfunction of dopamine and N-methyl-D-aspartate glutamate receptors that highlights N-methyl-D-aspartate receptor hypofunction as a key mechanism that can help explain major clinical and pathophysiological aspects of schizophrenia. The following fundamental features of schizophrenia are accommodated by this hypothesis: (1) the occurrence of structural brain changes during early development that have the potential for producing subsequent clinical manifestations of schizophrenia, (2) a quiescent period in infancy and adolescence before clinical manifestations are expressed, (3) onset in early adulthood of psychotic symptoms, (4) involvement of dopamine (D2) receptors in some cases but not others that would explain why some but not all patients are responsive to typical neuroleptic therapy, and (5) ongoing neurodegenerative changes and cognitive deterioration in some patients. We propose that since N-methyl-D-aspartate receptor hypofunction can cause psychosis in humans and corticolimbic neurodegenerative changes in the rat brain, and since these changes are prevented by certain antipsychotic drugs, including atypical neuroleptic agents (clozapine, olanzapine, fluperlapine), a better understanding of the N-methyl-D-aspartate receptor hypofunction mechanism and ways of preventing its neurodegenerative consequences in the rat brain may lead to improved pharmacotherapy in schizophrenia.
Akt/Protein Kinase B Inhibits Cell Death by Preventing the Release of Cytochrome c from Mitochondria (1999)

Growth factors signaling through the phosphoinositide 3-kinase/Akt pathway promote cell survival. The mechanism by which the serine/threonine kinase Akt prevents cell death remains unclear. We have previously shown that Akt inhibits the activity of DEVD-targeted caspases without changing the steady-state levels of Bcl-2 and Bcl-x(L). Here we show that Akt inhibits apoptosis and the processing of procaspases to their active forms by delaying mitochondrial changes in a caspase-independent manner. Akt activation is sufficient to inhibit the release of cytochrome c from mitochondria and the alterations in the inner mitochondrial membrane potential. However, Akt cannot inhibit apoptosis induced by microinjection of cytochrome c. We also demonstrated that Akt inhibits apoptosis and cytochrome c release induced by several proapoptotic Bcl-2 family members. Taken together, our results show that Akt promotes cell survival by intervening in the apoptosis cascade before cytochrome c release and caspase activation via a mechanism that is distinct from Bad phosphorylation.
Attenuation of anti-Thy1 glomerulonephritis in the rat by anti-inflammatory platelet-inhibiting agents. (1993)

Although both ecto-ADPase and prostacyclin (PGI2) inhibit platelets and neutrophils, their action in acute glomerulonephritis is unknown. We tested the PGI2 analog Iloprost and 2chloroadenosine (2Cl-ADO), an analog of adenosine, the end product of nucleotidase activities, during anti-Thy1 nephritis. Rats received anti-Thy1 immunoglobulin G (5 mg/kg body weight, intravenously) and subsequently one subcutaneous injection of either 2Cl-ADO (10 mg/kg body weight; (n = 6) or Iloprost (1 mg/kg body weight; n = 6). Control rats received anti-Thy1 immunoglobulin G with saline (n = 6) or saline alone (n = 6). After 24 hours, kidneys were processed for light-microscopical evaluation. Proteinuria was studied in additional rats. Results showed that both drugs inhibited intraglomerular platelet activation (P < 0.005). 2Cl-ADO also reduced intraglomerular O2- production of neutrophils (P < 0.05), in contrast to Iloprost. Intraglomerular immunoglobulin G deposition, complement activation, neutrophil influx, and myeloperoxidase release were not affected by 2Cl-ADO or Iloprost. However, proteinuria was completely prevented by both drugs. It is concluded that PGI2 and nucleotidases are potentially able to attenuate this form of nephritis by inhibiting platelet activity, whereas nucleotidases also inhibit neutrophil activity in vivo.