gebhart/patrepeval huggingface dataset:
Use of the short-acting insulin analogue lispro in intensive treatment of Type 1 diabetes mellitus: importance of appropriate replacement of basal insulin and time-interval injection-meal (1998)

To establish whether lispro may be a suitable short-acting insulin preparation for meals in intensive treatment of Type 1 diabetes mellitus (DM) in patients already in chronic good glycaemic control with conventional insulins, 69 patients on intensive therapy (4 daily s.c. insulin injections, soluble at each meal, NPH at bedtime, HbA1c <7.5%) were studied with an open, cross-over design for two periods of 3 months each (lispro or soluble). The % HbA1c and frequency of hypoglycaemia were assessed under four different conditions (Groups I-IV). Lispro was always injected at mealtime, soluble 10-40 min prior to meals (with the exception of Group IV). Bedtime NPH was continued with both treatments. When lispro replaced soluble with no increase in number of daily NPH injections (Group I, n = 15), HbA1c was no different (p = NS), but frequency of hypoglycaemia was greater (p < 0.05). When NPH was given 3-4 times daily, lispro (Group II, n = 18), but not soluble (Group III, n = 12) decreased HbA1c by 0.35 +/- 0.25% with no increase in hypoglycaemia. When soluble was injected at mealtimes, HbA1c increased by 0.18 +/- 0.15% and hypoglycaemia was more frequent than when soluble was injected 10-40 min prior to meals (Group IV, n = 24) (p < 0.05). It is concluded that in intensive management of Type 1 DM, lispro is superior to soluble in terms of reduction of % HbA1c and frequency of hypoglycaemia, especially for those patients who do not use a time interval between insulin injection and meal. However, these goals cannot be achieved without optimization of basal insulin.
Onset of Effect of 5‐HT 1B/1D Agonists: A Model With Pharmacokinetic Validation (2004)

Onset of effect is related to rate of absorption of sumatriptan. There is greater scope for improving onset of effect using an alternative route of administration than by increasing the oral dose.
Combined Effect of Nisin, Carvacrol and Thymol on the Viability of Bacillus Cereus Heat-Treated Vegetative Cells (2001)

The influence of mild heat pretreatment on the bactericidal action of nisin, carvacrol and thymol on stationary and exponential phase cells of two Bacillus cereus strains was studied. Carvacrol or thymol concentrations of 0.3 mmol/L had no bactericidal effect on unheated, and a minor effect on heated B. cereus cells either in stationary or exponential growth phases. Nisin (0.15 mg/mL) alone decreased the viable counts in all cases (unheated and heated cells in stationary and exponential phase) although the two strains tested showed different sensitivity to this natural antimicrobial between them. When carvacrol or thymol were combined with nisin, it resulted in a greater loss of viability of heated cells than when nisin was applied alone. There was a synergistic effect of nisin and both essential oils with a mild heat pretreatment on the viability of B. cereus cells. This study pointed out the potential use of nisin alone and in combination with carvacrol or thymol applied after a mild heat pretreatment for preservation of minimally processed foods.
Lipid hydroperoxide generation, turnover, and effector action in biological systems (1998)

Lipid peroxidation is a well known example of oxidative damage in cell membranes, lipoproteins, and other lipid-containing structures. Peroxidative modification of unsaturated phospholipids, glycolipids, and cholesterol can occur in reactions triggered by i) free radical species such as oxyl radicals, peroxyl radicals, and hydroxyl radicals derived from iron-mediated reduction of hydrogen peroxide or ii) non-radical species such as singlet oxygen, ozone, and peroxynitrite generated by the reaction of superoxide with nitric oxide. Lipid hydroperoxides (LOOHs) are prominent non-radical intermediates of lipid peroxidation whose identification can often provide valuable mechanistic information, e.g., whether a primary reaction is mediated by singlet oxygen or oxyradicals. Certain cholesterol-derived hydroperoxides (ChOOHs) have been used very effectively in this regard, both in model systems and cells. Being more polar than parent lipids, LOOHs perturb membrane structure/function and can be deleterious to cells on this basis alone. However, LOOHs can also participate in redox reactions, the nature and magnitude of which often determines whether peroxidative injury is exacerbated or prevented. Exacerbation may reflect iron-catalyzed one-electron reduction of LOOHs, resulting in free radical-mediated chain peroxidation, whereas prevention may reflect selenoperoxidase-catalyzed two-electron reduction of LOOHs to relatively non-toxic alcohols. LOOH partitioning between these two pathways in an oxidatively stressed cell is still poorly understood, but recent cell studies involving various ChOOHs have begun to shed light on this important question. An aspect of related interest that is under intensive investigation is lipid peroxidation/LOOH-mediated stress signaling, which may evoke a variety of cellular responses, ranging from induction of antioxidant enzymes to apoptotic death. Ongoing exploration of these processes will have important bearing on our understanding of disease states associated with peroxidative stress.
Hydrophobic proteins of lamellated osmiophilic bodies isolated from pig lung (1979)

1. In addition to proteins that are insoluble in organic solvents, lamellated bodies isolated from pig lung and surfactant prepared from bronchopulmonary lavage fluid contain another group of proteins that are extracted together with lipid into the organic phase. 2. These hydrophobic proteins constitute about 40% of the total protein of lamellated bodies and about 13% of the total protein of surfactant isolated from lavage fluid, whereas less than 1% of the total protein of pig lung microsomal fraction and mitochondria is extracted by organic solvents. 3. The hydrophobic proteins of lamellated bodies were separated into four fractions and freed from phospholipid by chromatographic procedures. Their apparent molecular weights vary between 11 500 and 16 500, they contain 72--79% of hydrophobic residues and 16--22% of sulphur-containing amino-acids, and leucine is the major N-terminal amino acid in each case.
Proximal Methods for Hierarchical Sparse Coding (2010)

Sparse coding consists in representing signals as sparse linear combinations of atoms selected from a dictionary. We consider an extension of this framework where the atoms are further assumed to be embedded in a tree. This is achieved using a recently introduced tree-structured sparse regularization norm, which has proven useful in several applications. This norm leads to regularized problems that are difficult to optimize, and we propose in this paper efficient algorithms for solving them. More precisely, we show that the proximal operator associated with this norm is computable exactly via a dual approach that can be viewed as the composition of elementary proximal operators. Our procedure has a complexity linear, or close to linear, in the number of atoms, and allows the use of accelerated gradient techniques to solve the tree-structured sparse approximation problem at the same computational cost as traditional ones using the L1-norm. Our method is efficient and scales gracefully to millions of variables, which we illustrate in two types of applications: first, we consider fixed hierarchical dictionaries of wavelets to denoise natural images. Then, we apply our optimization tools in the context of dictionary learning, where learned dictionary elements naturally organize in a prespecified arborescent structure, leading to a better performance in reconstruction of natural image patches. When applied to text documents, our method learns hierarchies of topics, thus providing a competitive alternative to probabilistic topic models.
[Non-neurogenic lower urinary tract dysfunction]. (2008)

Functional bladder disorders in children are a common condition and they are observed in 5-15% of pediatric population. Recent observations of bladder function of the healthy newborns have changed our viewpoint on its behaviour in older children. By the age of 4 years, many if not most children have matured their urinary tract function and developed an adult pattern of urinary control. They are generally dry during the day and the night. The adult pattern is characterized during bladder filling by an absence of unstable or uninhibited (involuntary) detrusor contractions. Urodynamic studies have confirmed that even at bladder capacity and when the desire to void is strong, detrusor contraction will not occur unless it is voluntarily initiated. The voiding symptoms and urinary incontinence or urinary infection and are thought to be caused by behavioral factors that affect toilet training and prevent successful transition from the infantile to the adult pattern of urinary control. These syndromes of dysfunctional elimination differ greatly in manifestation, prognosis, and pathophysiology and comprise a clinical spectrum that varies widely. At the severe end of the spectrum are a small group of patients with Hinman's syndrome, also termed the non-neurogenic neurogenic bladder, dysfunctional voiding, or occult neuropathic bladder. Less severe uropathology is observed in the large group of children who present with refractory and often severe symptoms that reflect incomplete toilet training with diminished urinary control. Their obstruction is caused by an incoordination between bladder and sphincter that occurs only during bladder filling in the presence of unstable bladder contractions and is, therefore, of less potential risk to the urinary tract. Unstable bladder, the most common pattern of urinary dysfunction in childhood, occurs in up to 57% of symptomatic children aged 3 to 14 years. Voluntary constriction of the urinary sphincter during unstable bladder contractions produces urinary obstruction with high intravesical pressures. The assessment of children with lower urinary tract disorders should consist of a detailed history, a frequency/volume chart and a physical examination. Uroflowmetry and ultrasound examination can be added. Treatment of functional bladder disorders in children can be divided in urotherapy, consisting of standard therapy and some specialized types of urotherapy like biofeedback, neuromodulation, pharmacotherapy and botulinum toxin injections.
Regulation of ICAM-1 expression and function in human dermal fibroblasts by IL-4 (1992)

ICAM-1 is found on the surface of many hematopoietic and nonhematopoietic cells and can function as an adhesive ligand for the integrin, leukocyte function-associated molecule-1 (LFA-1, CD11a/CD18). ICAM-1/leukocyte function-associated molecule-1 interaction has been shown to be of importance in many immune-mediated cell-cell adhesion reactions. In vitro, unstimulated human fibroblast cell cultures express low levels of ICAM-1. Using ELISA, cytofluorography, electron microscopy, Northern analysis, and an in vitro cell adherence assay, we demonstrate that treatment of human dermal fibroblasts with the cytokine IL-4 leads to an increase in cell surface ICAM-1 expression that is under transcriptional control as well as increased fibroblast adhesion to LFA-1-bearing T lymphocytes. The kinetics of increased ICAM-1 expression induced by IL-4 paralleled the increase in ICAM-1-dependent T lymphocyte adhesion. The increase in T cell adhesion was determined to be due to the effects of IL-4 on the fibroblasts and not the adhering T cells. Treatment of fibroblasts with IL-4 also resulted in enhanced binding of human rhinovirus, a recently reported additional ligand for ICAM-1. Virus binding was IL-4 dose dependent and could be inhibited with mAb to ICAM-1. Both the expression of ICAM-1 and the ICAM-1-dependent increase in T lymphocyte adhesion that was induced by IL-4 could be inhibited by preexposure of the fibroblasts to either IL-1 or IL-6, suggesting that multiple cytokines can have both positive and negative effects on human fibroblast ICAM-1 expression and function.
Analysis of Proteins by Direct-Scanning Infrared- MALDI Mass Spectrometry after 2D-PAGE Separation and Electroblotting (1997)

A novel approach is reported for the analysis and identification of proteins separated by 2D-PAGE with scanning infrared matrix-assisted laser desorption/ionization mass spectrometry (scanning IR-MALDI-MS). The proteins of human blood plasma were separated by 2D-PAGE, electroblotted onto PVDF membranes, incubated in matrix solution, and then scanned by IR-MALDI-MS. Mass contour plots of selected spots were obtained. Protein separation is shown to be conserved by comparison with silver-stained gels. The sensitivity for the protein detection is comparable if not better than that of silver-stained gels. Posttranslational modifications were identified by comparing the measured mass to the one calculated from the known DNA sequence. Adduct formation to unprotected cysteine residues during gel separation is demonstrated for selected proteins.
TNFα plus IFNγ induce the production of Alzheimer β‐amyloid peptides and decrease the secretion of APPs (1999)

The appearance of inflammatory markers associated with amyloid plaques indicates a state of chronic inflammation in Alzheimer's disease (AD). Multiple epidemiological studies also suggest that patients taking anti-inflammatory drugs have a decreased risk of developing AD. Here we present evidence that inflammatory cytokines can alter the metabolism of the beta-amyloid precursor protein (betaAPP). We show that the combination of tumor necrosis factor alpha and interferon gamma triggers the production of beta-amyloid peptides and inhibits the secretion of soluble APPs by human neuronal and extraneuronal cells. The results demonstrate a new mechanism by which inflammatory components can exacerbate the fundamental pathology in AD.
Molecular cloning and tissue distribution of a putative member of the rat opioid receptor gene family that is not a μ, δ or κ opioid receptor type (1994)

A novel G protein-coupled receptor was cloned by PCR and homology screening. Its deduced amino acid sequence is 47% identical overall to the mu, delta and kappa opioid receptors and 64% identical in the putative transmembrane domains. When transiently expressed in COS-7 cells this receptor did not bind any of the typical mu, delta or kappa opioid receptor ligands with high affinity. In situ hybridization analysis revealed that LC132 mRNA is highly expressed in several rat brain areas, including the cerebral cortex, thalamus, subfornical organ, habenula, hypothalamus, central gray, dorsal raphe, locus coeruleus and the dorsal horn of the spinal cord. Based on this distribution and its high homology with the mu, delta and kappa opioid receptors, it is proposed that LC132 is a new member of the opioid receptor family that is involved in analgesia and the perception of pain.
A Phase Ib Study of Alpelisib (BYL719), a PI3Kα-Specific Inhibitor, with Letrozole in ER+/HER2− Metastatic Breast Cancer (2016)

Alpelisib's maximum-tolerated dose (MTD) in combination with letrozole was 300 mg/d. Common drug-related adverse events included hyperglycemia, nausea, fatigue, diarrhea, and rash with dose-limiting toxicity occurring at 350 mg/d of alpelisib. The clinical benefit rate (lack of progression ≥6 months) was 35% (44% in patients with PIK3CA-mutated and 20% in PIK3CA wild-type tumors; 95% CI, 17%-56%), including five objective responses. Of eight patients remaining on treatment ≥12 months, six had tumors with a PIK3CA mutation. Among evaluable tumors, those with FGFR1/2 amplification and KRAS and TP53 mutations did not derive clinical benefit. Overexpression of FGFR1 in ER<sup>+</sup>/PIK3CA mutant breast cancer cells attenuated the response to alpelisib in vitro CONCLUSIONS: The combination of letrozole and alpelisib was safe, with reversible toxicities. Clinical activity was observed independently of PIK3CA mutation status, although clinical benefit was seen in a higher proportion of patients with PIK3CA-mutated tumors. Phase II and III trials of alpelisib and endocrine therapy in patients with ER<sup>+</sup> breast cancer are ongoing. Clin Cancer Res; 23(1); 26-34. ©2016 AACR.
Quantitative MRI establishes the efficacy of PI3K inhibitor (GDC-0941) multi-treatments in PTEN-deficient mice lymphoma. (2012)

This protocol can accommodate complex dosing schedules, as well as combine different cancer therapies. It reduces biological variability problems and resulted in a 10-fold reduction in mouse numbers compared with terminal assessment methods. It is ideal for preclinical efficacy studies and for phenotyping molecularly characterized mouse models when investigating gene function.
Implementing poultry vaccination and biosecurity at the village level in Tanzania: a social strategy to promote health in free-range poultry populations (2009)

A social strategy was tested for implementing Newcastle disease (ND) vaccination and biosecurity improvements among free-ranging chicken at village level in Tanzania. In addition to training the local poultry vaccinators, data recorders and poultry-keepers, the strategy involved training and empowering leaders at the district, ward and village level. The trainings covered poultry health, management, and marketing of village chickens, with an emphasis on ND vaccination and improving biosecurity against avian influenza (AI), The study sites included villages in one ward in each of three each three districts (Iringa, Mtwara-Mikindani, and Mvomero) of mainland Tanzania. Ninety-six local leaders at district level and 101 leaders at ward levels were trained. In addition, 196 farmers (households) were trained, as well as 86 vaccinators and 26 data recorders. Data recorders were also trained as poultry first aid workers. ND vaccination was conducted by the vaccinators, supervised by their local leaders with technical assistance from veterinarians. A total of 158,343 village chickens were vaccinated in three rounds of vaccination three months apart. The training and empowerment of local leaders and local implementers was the key element for success as it fostered the feeling of local ownership of the program and prevented conflicts with other development activities within the villages. We conclude that most animal health programs will increase their odds of success by involving local leaders and by addressing the current challenges facing the farmers. Further assessment on the usefulness of this approach is needed.
Not Just Another Voice Mail System (1991)

Telephone keypad interfaces are commonly used for interacting with voice mail systems whether one is at home or in the office. Typically, after new messages are heard by the recipient, they are transferred to an archived voice mailbox. Management of messages inside the mailbox is difficult due to the limited interaction available from a 12 button interface. Users often need to recall seemingly arbitrary assignments of functions to keys. An enhanced
Feedback regulation of plastidic acetyl-CoA carboxylase by 18:1-acyl carrier protein in Brassica napus (2012)

Plant seed oil represents a major renewable source of reduced carbon, but little is known about the biochemical regulation of its synthesis. The goal of this research was to identify potential feedback regulation of fatty acid biosynthesis in Brassica napus embryo-derived cell cultures and to characterize both the feedback signals and enzymatic targets of the inhibition. Fatty acids delivered via Tween esters rapidly reduced the rate of fatty acid synthesis in a dose-dependent and reversible manner, demonstrating the existence of feedback inhibition in an oil-accumulating tissue. Tween feeding did not affect fatty acid elongation in the cytosol or the incorporation of radiolabeled malonate into nascent fatty acids, which together pinpoint plastidic acetyl-CoA carboxylase (ACCase) as the enzymatic target of feedback inhibition. To identify the signal responsible for feedback, a variety of Tween esters were tested for their effects on the rate of fatty acid synthesis. Maximum inhibition was achieved upon feeding oleic acid (18:1) Tween esters that resulted in the intracellular accumulation of 18:1 free fatty acid, 18:1-CoA, and 18:1-acyl-carrier protein (ACP). Direct, saturable inhibition of ACCase enzyme activity was observed in culture extracts and in extracts of developing canola seeds supplemented with 18:1-ACP at physiological concentrations. A mechanism for feedback inhibition is proposed in which reduced demand for de novo fatty acids results in the accumulation of 18:1-ACP, which directly inhibits plastidic ACCase, leading to reduced fatty acid synthesis. Defining this mechanism presents an opportunity for mitigating feedback inhibition of fatty acid synthesis in crop plants to increase oil yield.
Imaging Studies of Patients with Malignant Fibrous Histiocytoma Using C-11-Alpha-Aminoisobutyric Acid (AIB) (1987)

Alpha-aminoisobutyric acid (AIB), a synthetic, nonmetabolized amino acid which is rapidly transported into viable cells by the A-type or alanine-preferring amino acid transport system, has been labeled with the short-lived, positron-emitting radionuclide carbon-11. Carbon-11 labeled AIB is currently being evaluated as a tumor imaging agent for in vivo amino acid transport studies in patients with cancer. In this study, C-11 AIB was used to image two patients with malignant fibrous histiocytoma (MFH), a pleomorphic sarcoma. Following intravenous administration of C-11 AIB, tumors in the distal femur of one patient and in the anterior chest wall of another patient were well visualized using high energy gamma scintigraphy. Since therapy may alter the accumulation of amino acids in tumor tissue, studies using C-11 AIB in patients with MFH before and after chemotherapy are in progress.
Nanoscale silicon field effect transistors fabricated using imprint lithography (1997)

We report the fabrication and characterization of nanoscale silicon field effect transistors using nanoimprint lithography. With this lithographic technique and dry etching, we have patterned a variety of nanoscale transistor features in silicon, including 100 nm wire channels, 250-nm-diam quantum dots, and ring structures with 100 nm ring width, over a 2×2 cm lithography field with good uniformity. Compared with devices fabricated by the conventional electron-beam lithography, we did not observe any degradation in the device characteristics. The successful fabrication of the semiconductor nanodevices represents a step forward to make nanoimprint lithography a viable technique for the mass production of semiconductor devices.
New Approaches to Radiation Protection (2015)

Radioprotectors are compounds that protect against radiation injury when given prior to radiation exposure. Mitigators can protect against radiation injury when given after exposure but before symptoms appear. Radioprotectors and mitigators can potentially improve the outcomes of radiotherapy for cancer treatment by allowing higher doses of radiation and/or reduced damage to normal tissues. Such compounds can also potentially counteract the effects of accidental exposure to radiation or deliberate exposure (e.g., nuclear reactor meltdown, dirty bomb, or nuclear bomb explosion); hence they are called radiation countermeasures. Here, we will review the general principles of radiation injury and protection and describe selected examples of radioprotectors/mitigators ranging from small-molecules to proteins to cell-based treatments. We will emphasize agents that are in more advanced stages of development.