gebhart/patrepeval huggingface dataset:
Survival and Failure Patterns of High-Grade Gliomas After Three-Dimensional Conformal Radiotherapy (2002)

PURPOSE: The goal of three-dimensional (3-D) conformal radiation is to increase the dose delivered to tumor while minimizing dose to surrounding normal brain. Previously it has been shown that even escalated doses of 70 to 80 Gy have failure patterns that are predominantly local. This article describes the failure patterns and survival seen with high-grade gliomas given 90 Gy using a 3-D conformal intensity-modulated radiation technique. PATIENTS AND METHODS: From April 1996 to April 1999, 34 patients with supratentorial high-grade gliomas were treated to 90 Gy. For those that recurred, failure patterns were defined in terms of percentage of recurrent tumor located within the high-dose region. Recurrences with more than 95% of their volume within the high-dose region were considered central; those with 80% to 95%, 20% to 80%, and less than 20% were considered in-field, marginal, and distant, respectively. RESULTS: The median age was 55 years, and median follow-up was 11.7 months. At time of analysis, 23 (67.6%) of 34 patients had developed radiographic evidence of recurrence. The patterns of failure were 18 (78%) of 23 central, three (13%) of 23 in-field, two (9%) of 23 marginal, and zero (0%) of 23 distant. The median survival was 11.7 months, with 1-year survival of 47.1% and 2-year survival of 12.9%. No significant treatment toxicities were observed. CONCLUSION: Despite dose escalation to 90 Gy, the predominant failure pattern in high-grade gliomas remains local. This suggests that close margins used in highly conformal treatments do not increase the risk of marginal or distant recurrences. Our results indicate that intensification of local radiotherapy with dose escalation is feasible and deserves further evaluation for high-grade gliomas.
Unequal Efficacy of Pyridinium Oximes in Acute Organophosphate Poisoning (2007)

The use of organophosphorus pesticides results in toxicity risk to non-target organisms. Organophosphorus compounds share a common mode of action, exerting their toxic effects primarily via acetylcholinesterase (AChE) inhibition. Consequently, acetylcholine accumulates in the synaptic clefts of muscles and nerves, leading to overstimulation of cholinergic receptors. Acute cholinergic crisis immediately follows exposure to organophosphate and includes signs and symptoms resulting from hyperstimulation of central and peripheral muscarinic and nicotinic receptors. The current view of the treatment of organophosphate poisoning includes three strategies, i.e. the use of an anticholinergic drug (e.g., atropine), cholinesterase-reactivating agents (e.g., oximes) and anticonvulsant drugs (e.g., benzodiazepines). Oximes, as a part of antidotal therapy, ensure the recovery of phosphylated enzymes via a process denoted as reactivation of inhibited AChE. However, both experimental results and clinical findings have demonstrated that different oximes are not equally effective against poisonings caused by structurally different organophosphorus compounds. Therefore, antidotal characteristics of conventionally used oximes can be evaluated regarding how close the certain substance is to the theoretical concept of the universal oxime. Pralidoxime (PAM-2), trimedoxime (TMB-4), obidoxime (LüH-6), HI-6 and HLö-7 have all been demonstrated to be very effective in experimental poisonings with sarin and VX. TMB-4 and LüH-6 may reactivate tabun-inhibited AChE, whereas HI-6 possesses the ability to reactivate the soman-inhibited enzyme. An oxime HLö-7 seems to be an efficient reactivator of AChE inhibited by any of the four organophosphorus warfare agents. According to the available literature, the oximes LüH-6 and TMB-4, although relatively toxic, are the most potent to induce reactivation of AChE inhibited by the majority of organophosphorus pesticides. Since there are no reports of controlled clinical trials on the use of TMB-4 in human organophosphate pesticide poisoning, LüH-6 may be a better option.
Interfaces for strongly-typed object-oriented programming (1989)

This paper develops a system of explicit interfaces for object-oriented programming. The system provides the benefits of module interfaces found in languages like Ada and Modula-2 while preserving the expressiveness that gives untyped object-oriented languages like Smalltalk their flexibility. Interfaces are interpreted as polymorphic types to make the system sufficiently powerful. We use interfaces to analyze the properties of inheritance, and identify three distinct kinds of inheritance in object-oriented programming, corresponding to objects, classes, and interfaces, respectively. Object interfaces clarify the distinction between interface containment and inheritance and give insight into limitations caused by equating the notions of type and class in many typed object-oriented programming languages. Interfaces also have practical consequences for design, specification, and maintenance of object-oriented systems.
Replantation of 400 avulsed permanent incisors. 3. Factors related to root growth (1995)

Four hundred avulsed and replanted permanent incisors were examined for pulpal and periodontal healing. In 30 teeth, root formation was incomplete at the time of injury. Two teeth were excluded from the study due to nonphysiological extraalveolar storage (i.e. homemade saline). Of the 28 remaining replanted incisors, 7 showed subsequently completed root development, 8 partially completed root development and 13 arrested root development. Completed root development subsequent to replantation was found to be significantly related to pulpal revascularization, being rare in cases with pulp necrosis (5 of 15 teeth) and frequent after pulpal healing (11 of 13 teeth) (p = 0.01). Root development was not found to be significantly related to the extraalveolar storage period; but occurred slightly more frequently when the dry storage period was less than 45 min. (p = 0.13). Ingrowth of bone and formation of an internal periodontal ligament (PDL) was found in 6 teeth and was related to arrested root formation in cases with pulpal healing. The explanatory factor for these findings appeared to be damage to the Hertwig's epithelial root sheath.
Static branch frequency and program profile analysis (1994)

Program profiles identify frequently executed portions of a program, which are the places at which optimizations offer programmers and compilers the greatest benefit. Compilers, however, infrequently exploit program profiles, because profiling a program requires a programmer to instrument and run the program. An attractive alternative is for the compiler to statically estimate program profiles. This paper presents several new techniques for static branch prediction and profiling. The first technique combines multiple predictions of a branch's outcome into a prediction of the probability that the branch is taken. Another technique uses these predictions to estimate the relative execution frequency (i.e., profile) of basic blocks and control-flow edges within a procedure. A third algorithm uses local frequency estimates to predict the global frequency of calls, procedure invocations, and basic block and control-flow edge executions. Experiments on the SPEC92 integer benchmarks and Unix applications show that the frequently executed blocks, edges, and functions identified by our techniques closely match those in a dynamic profile.
PbTe quantum dot doped glasses with absorption edgeinthe 1.5 µm wavelength region (1995)

PbTe nanocrystals have been grown in doped glasses. By choosing the appropriate glass matrix and controlling the heat treatment temperatures and times, the quantum confined energy gaps of the PbTe dots can be changed in the wavelength range 1.1 – 2.0 µm. These glasses are potential materials for applications in optical communication and optoelectronic devices.
Altered patterns of gap junction distribution in ischemic heart disease. An immunohistochemical study of human myocardium using laser scanning confocal microscopy. (1991)

Arrhythmias are a common and potentially life-threatening complication of myocardial ischemia and infarction in humans. The structural pathways for the rapid intercellular conduction of the electrical impulse that stimulates coordinated contraction in the myocardium are formed by the gap junctions situated at intercalated disks. By raising antibodies to cardiac gap-junctional protein, and using these antibodies in an immunohistochemical procedure in combination with the technique of laser scanning confocal microscopy, we have succeeded in localizing gap junctions, with a clarity not previously possible, through thick volumes of human myocardial tissue. To explore the structural basis for ischemia and infarction-related arrhythmogenesis, antibody labeling and laser scanning confocal microscopy were applied to study the organization, distribution, and other characteristics of gap junctions in the explanted hearts of patients undergoing cardiac transplantation for advanced ischemic heart disease. In areas of myocardium free from histologically detectable structural damage, there was no significant difference in the size of distribution of labeled gap junctions, or in their number per intercalated disk, between left ventricular tissue (in which functional impairment was severe) and right ventricular tissue (in which functional impairment was minimal). However, in myocytes at the border of healed infarcts--zones to which the slow conduction responsible for reentry arrhythmias has been localized--the organization of gap junctions was markedly disordered; instead of being aggregated into discrete intercalated disks, gap-junctional immunostaining was spread extensively over myocyte surfaces. Some infarct zones were bridged by continuous strands of myocytes, coupled to one another by gap junctions, thereby linking healthy myocardium on either side. At their thinnest, these bridges were in some instances no wider than a single attenuated myocyte. The conclusions are 1) a widespread, generalized derangement of gap junction organization does not appear to underlie functional impairment in the ischemic heart, 2) a disorderly arrangement typifies gap junctions in myocytes of the infarct border zone, and this may contribute to alterations in conduction that are capable of precipitating reentry arrhythmias, and 3) delicate chains of myocytes traverse some healed infarcts, apparently forming electrically coupled bridges across what would otherwise constitute blocked zones. The weakest link in this chain can be a single, degenerating myocyte; avoidance of arrhythmia may therefore depend on the continued survival of this single cell.
The Effect of Enzymatic Alcoholysis on the Physicochemical Properties of Commercial Cocoa Butter Substitutes (2011)

The need for low-calorie fats has increased because of recent changes in consumers' concerns about leading healthier lifestyles. Three types of commercial Cocoa Butter Substitutes (CBSs) were studied for use as substrates in the production of low-calorie structured lipids. Mixtures of commercial CBSs, ethanol and medium-chain fatty acids in a molar ratio of 1:2:1 were incubated in a water bath at 50 C for 24 h at 250 o rpm, using 10% immobilized lipase as a catalyst. The following physicochemical properties were determined before and after enzymatic alcoholysis: the Solid Fat Content (SFC), the slip melting point, the iodine value, the free fatty acid content, the thermal behavior and the fatty acid composition. Hisomel CBSs was chosen as a substrate for further analysis because of its sharp melting profile between room temperature (25 C) and o
Guidelines of Diagnostics and Treatment of Acute Left-Sided Colonic Diverticulitis (2013)

Males first admitted when less than 50 years of age undergo more primary operations and develop more recurrences of diverticular disease than do older people. Based on our data, however, we recommend surgery for all patients after two episodes of acute diverticulitis that resolves after conservative treatment with antibiotics.
The interaction of small domains between the subunits of phosphatidylinositol 3-kinase determines enzyme activity. (1994)

Previous studies have suggested that the two subunits of phosphatidylinositol (PI) 3-kinase, p85 and p110, function as localizing and catalytic subunits, respectively. Using recombinant p85 and p110 molecules, we have reconstituted the specific interaction between the two subunits of mouse PI 3-kinase in cells and in vitro. We have previously shown that the region between the two Src homology 2 (SH2) domains of p85 is able to form a functional complex with the 110-kDa subunit in vivo. In this report, we identify the corresponding domain in p110 which directs the binding to p85. We demonstrate that the interactive domains in p85 and p110 are less than 103 and 124 amino acids, respectively, in size. We also show that the association of p85 and p110 mediated by these domains is critical for PI 3-kinase activity. Surprisingly, a complex between a 102-amino-acid segment of p85 and the full-length p110 molecule is catalytically active, whereas p110 alone has no activity. In addition to the catalytic domain in the carboxy-terminal region, 123 amino acids at the amino terminus of p110 were required for catalytic activity and were sufficient for the interaction with p85. These results indicate that the 85-kDa subunit, previously thought to have only a linking role in localizing the p110 catalytic subunit, is an important component of the catalytic complex.
Enhanced production of biologically active interleukin‐1α and interleukin‐1β by psoriatic epidermal cells ex vivo: evidence of increased cytosolic interleukin‐1β levels and facilitated interleukin‐1 release (1995)

The expression of interleukin (IL)-1 is altered in psoriatic lesions. However, little is known about the actual production of IL-1 alpha and IL-1 beta by psoriatic epidermal cells (EC). We monitored IL-1 in the extracellular, the membrane and the intracellular compartment of freshly isolated EC from untreated lesional psoriatic (PP) and normal healthy (NN) skin during non-stimulated short-term cultures, representing a psoriasis model ex vivo. Cytokines were measured using bioassays combined with neutralizing antibodies and enzyme-linked immunosorbent assay in parallel. PP EC released significantly increased amounts of biologically active IL-1 alpha and IL-1 beta in a ratio of 3:1, whereas NN EC only released IL-1 alpha. Also, the release of IL-6, but not of TNF-alpha, by PP EC was significantly increased. Membrane-associated IL-1 activity, analyzed using glutaraldehyde-fixed EC, was low and not unique to PP EC. The cytosol of PP EC contained significantly increased levels of immunoreactive IL-1 beta. Furthermore, PP EC displayed loss of membrane integrity, as determined by trypan blue exclusion and release of cytosolic lactate dehydrogenase. This facilitated release of intracellular IL-1. Depletion of CD45+ cells showed that intraepidermal leukocytes did not contribute to the production of IL-1. Our observations show that resident PP EC express enhanced IL-1 production ex vivo, which is due to an increased cytosolic IL-1 beta content and facilitated IL-1 release. This study provides the first evidence that PP EC can produce bioactive IL-1 beta.
Diet and microbiota in inflammatory bowel disease: The gut in disharmony (2017)

Bacterial colonization of the gut shapes both the local and the systemic immune response and is implicated in the modulation of immunity in both healthy and disease states. Recently, quantitative and qualitative changes in the composition of the gut microbiota have been detected in Crohn's disease and ulcerative colitis, reinforcing the hypothesis of dysbiosis as a relevant mechanism underlying inflammatory bowel disease (IBD) pathogenesis. Humans and microbes have co-existed and co-evolved for a long time in a mutually beneficial symbiotic association essential for maintaining homeostasis. However, the microbiome is dynamic, changing with age and in response to environmental modifications. Among such environmental factors, food and alimentary habits, progressively altered in modern societies, appear to be critical modulators of the microbiota, contributing to or co-participating in dysbiosis. In addition, food constituents such as micronutrients are important regulators of mucosal immunity, with direct or indirect effects on the gut microbiota. Moreover, food constituents have recently been shown to modulate epigenetic mechanisms, which can result in increased risk for the development and progression of IBD. Therefore, it is likely that a better understanding of the role of different food components in intestinal homeostasis and the resident microbiota will be essential for unravelling the complex molecular basis of the epigenetic, genetic and environment interactions underlying IBD pathogenesis as well as for offering dietary interventions with minimal side effects.
Optimization of dynamic query evaluation plans (1994)

Traditional query optimizers assume accurate knowledge of run-time parameters such as selectivities and resource availability during plan optimization, i.e., at compile time. In reality, however, this assumption is often not justified. Therefore, the “static” plans produced by traditional optimizers may not be optimal for many of their actual run-time invocations. Instead, we propose a novel optimization model that assigns the bulk of the optimization effort to compile-time and delays carefully selected optimization decisions until run-time. Our previous work defined the run-time primitives, “dynamic plans” using “choose-plan” operators, for executing such delayed decisions, but did not solve the problem of constructing dynamic plans at compile-time. The present paper introduces techniques that solve this problem. Experience with a working prototype optimizer demonstrates (i) that the additional optimization and start-up overhead of dynamic plans compared to static plans is dominated by their advantage at run-time, (ii) that dynamic plans are as robust as the “brute-force” remedy of run-time optimization, i.e., dynamic plans maintain their optimality even if parameters change between compile-time and run-time, and (iii) that the start-up overhead of dynamic plans is significantly less than the time required for complete optimization at run-time. In other words, our proposed techniques are superior to both techniques considered to-date, namely compile-time optimization into a single static plan as well as run-time optimization. Finally, we believe that the concepts and technology described can be transferred to commercial query optimizers in order to improve the performance of embedded queries with host variables in the query predicate and to adapt to run-time system loads unpredictable at compile time.
Inhibition of Calcitonin Gene-related Peptide (CGRP) has the Potential to Extend First-phase Insulin Secretion (2013)

The neuropeptide calcitonin gene-related peptide (CGRP), known to have a strong vasodilation effect, has also been reported to inhibit insulin secretion. However, the physiological effect of CGRP related to insulin secretion is still unknown. Here, we evaluated the effect of whole-body CGRP inhibition by anti-CGRP antibodies in mice using an oral glucose tolerance test. CGRP has 2 isotypes, alpha-CGRP and beta-CGRP, and we confirmed the antibody used in this study inhibits function of both. Then, we evaluated the effect of CGRP inhibition on insulin secretion and discovered that CGRP inhibition lead to extend first-phase insulin secretion in an antibody dose-dependent manner and nearly plateaued at 10 mg/kg, although the effect was not so large and didn't affect plasma glucose level. We then measured the plasma antibody concentration and it was increased depending on administration dose. So, the effect of first-phase insulin secretion extension was determined to be the result of complete inhibition of CGRP by the antibody. These results indicate that CGRP has the potential to inhibit insulin secretion and shorten first-phase insulin secretion. However the effect of CGRP inhibition was not so large at least on healthy condition, and it indicates the effect of CGRP related to insulin secretion on healthy physiological condition may be limited.
Recognition Sites of 3′-OH Group by T7 RNA Polymerase and Its Application to Transcriptional Sequencing (1998)

When analyzing the elongation mechanisms in T7 RNA polymerase (T7 RNAP)by using site-directed mutagenesis and a protein expression system, we identified the recognition sites of the rNTP 3'-OH group in T7 RNAP. On the basis of three-dimensional crystal structure analysis, we selected and analyzed six candidate sites interacting with the 3'-OH group of rNTP in T7 RNAP. We found that the Phe-644 and Phe-667 sites are responsible for the high selectivity of T7 RNAP for rNTPs. Also, we constructed the protein mutations of these residues, F644Y and F667Y, which display a >200-fold higher affinity than the wild type for 3'-dNTPs. These findings indicate that the phenylalanine residues of 644 and 667 specifically interact with the 3'-OH group. Thus, these mutants, F644Y and F667Y, with incorporation of 3'-dNTP terminators, which is similar to native rNTPs, can offer low backgrounds and equal intensities of the sequencing ladders in our method, called "transcriptional sequencing. "
Side Effects of Antiepileptics— A Review (2004)

Older generation antiepileptic drugs like Phenobarbital (Luminal), carbamazepine (Tegretol), phenytoin (Dilantin), and valproic acid (Depakote) have several shortcomings such as suboptimal response rates, significant adverse effects, several drug interactions, and a narrow therapeutic index. New antiepileptic drugs have been developed in the last decade to overcome some of these problems. These newer generation antiepileptics like felbamate (Felbatol), gabapentin (Neurontin), lamotrigine (Lamictal), levetiracetam (Keppra), oxcarbazepine (Trileptal), tiagabine (Gabitril), topiramate (Topamax), and zonisamide (Zonegran) have better tolerability profiles, low interaction potential, and significantly less enzyme inducing or inhibiting properties. As the use of antiepileptic drugs has expanded to include treatment of neuropathic pain, newer side effects have been reported. In addition to the common side effects of antiepileptic drugs, like dizziness, drowsiness, and mental slowing; other side effects like weight gain, metabolic acidosis, nephrolithiasis, angle closure glaucoma, skin rash, hepatotoxicity, colitis, and movement and behavioral disorders, to name a few, have been brought to our attention. This review is an attempt to highlight the features and incidences of some of these side effects.