gebhart/patrepeval huggingface dataset:
Rheumatoid Arthritis (1990)

IN 1947, a technician who had rheumatoid arthritis and who worked in the laboratory of Dr. Harry Rose at Columbia University discovered that her own serum agglutinated excessively. Dr. Rose suggested that this serologic reaction might have been caused by the arthritis. Charles Ragan, a rheumatologist, pursued this suggestion and developed the sheep-cell agglutination test,1 , 2 which we know as a test for rheumatoid factor. For the first time, physicians had a key to the black box that was rheumatoid arthritis and could begin to study the immunologic abnormalities in patients with the disease. The classification of patients could also begin; . . .
EFFECTS OF HALOPERIDOL ON CELL PROLIFERATION IN THE EARLY POSTNATAL RAT BRAIN (1982)

Haloperidol, a widely used neuroleptic, produced a significant depression of the rate of [3H]thymidine incorporation into the DNA of 11-day-old rat brain. The reduction of in-vivo DNA synthesis rate was detectable by 4 h after subcutaneous injection of a single dose of haloperidol (20 mg/kg) and through the period 10-24 h after drug treatment the rate was less than 50% of that of controls in the forebrain. [3H]Thymidine incorporation returned to control values by 32 h. The effect on the cerebellum was similar but less pronounced. The depression was dose-dependent and a half-maximal effect was produced with haloperidol doses of 5-10 mg/kg. Parallel histological studies on treated rats suggested prolongation of the DNA synthesis phase of the cell cycle in the forebrain subependymal layer, associated with an increase in turnover time of about 15%.
Cytokinin Effects on Creeping Bentgrass Responses to Heat Stress: I. Shoot and Root Growth (2002)

Heat stress injury may involve inhibition of cytokinin biosynthesis in roots. The objective of this study was to examine whether application of a synthetic cytokinin, zeatin riboside (ZR), to the root zone would enhance tolerance of creeping bentgrass ( Agrostis palustris L.) to high soil temperature or in combination with high air temperature. Grasses were exposed to three air and soil temperature regimes for 56 d in growth chambers: (i) optimum air and soil temperature (control), 20/20°C; (ii) optimum air but high soil temperature (20/35°C); and (iii) high air and soil temperatures (35/35°C). Four concentrations (0.01, 0.1, 1, and 10 μmol) of ZR or water (control) were injected into the 0–5 cm root zone on the day before heat stress (0 d) and 14 d after. Turf visual quality, canopy net photosynthetic rate (P n ), leaf photochemical efficiency (Fv/Fm), and vertical shoot extension rate decreased, whereas root mortality and root electrolyte leakage increased at 20/35 and 35/35°C, and to a greater extent at 35/35°C. Applications of 1 and 10 μmol ZR mitigated heat stress injury to shoots and roots during most of the experimental period, with 10 μmol ZR being more effective when applied at either 0 or 14 d of heat stress. Application of 0.1 μmol ZR was less effective than 1 and 10 μmol ZR. Application of 0.01 μmol ZR had no effects on shoot and root responses to high soil temperature alone or combined with high air temperature. Endogenous cytokinin content in both shoots and roots increased with the application of 1 and 10 μmol ZR. These results demonstrated that applying ZR at 1 or 10 μmol concentration to the root zone could alleviate heat stress injury of creeping bentgrass.
The Kynurenine Pathway in Brain Tumor Pathogenesis (2012)

Abstract Brain tumors are among the most common and most chemoresistant tumors. Despite treatment with aggressive treatment strategies, the prognosis for patients harboring malignant gliomas remains dismal. The kynurenine pathway (KP) is the principal route of l-tryptophan catabolism leading to the formation of the essential pyridine nucleotide, nicotinamide adenine dinucleotide (NAD+), and important neuroactive metabolites, including the neurotoxin, quinolinic acid (QUIN), the neuroprotective agent, picolinic acid (PIC), the TH17/Treg balance modulator, 3-hydroxyanthranilic acid (3-HAA), and the immunosuppressive agent, l-Kynurenine (KYN). This review provides a new perspective on KP dysregulation in defeating antitumor immune responses, specifically bringing light to the lower segment of the KP, particularly QUIN-induced neurotoxicity and downregulation of the enzyme α-amino-β-carboxymuconate-ϵ-semialdehyde decarboxylase (ACMSD) as a potential mechanism of tumor progression. Given its immunosuppressive effects, 3-HAA produced from the KP may also play a role in suppressing antitumor immunity in human tumors. The enzyme indoleamine 2, 3-dioxygenase (IDO-1) initiates and regulates the first step of the KP in most cells. Mounting evidence directly implicates that the induction and overexpression of IDO-1 in various tumors is a crucial mechanism facilitating tumor immune evasion and persistence. Tryptophan 2, 3-dioxygenase (TDO-2), which initiates the same first step of the KP as IDO-1, has likewise recently been shown to be a mechanism of tumoral immune resistance. Further, it was also recently shown that TDO-2–dependent production of KYN by brain tumors might be a novel mechanism for suppressing antitumor immunity and supporting tumor growth through the activation of the Aryl hydrocarbon receptor (AhR). This newly identified TDO-2-KYN-AhR signaling pathway opens up exciting future research opportunities and may represent a novel therapeutic target in cancer therapy. Our discussion points to a number of KP components, namely TDO-2, IDO-1, and ACMSD, as important therapeutic targets for the treatment of brain cancer. Targeting the KP in brain tumors may represent a viable strategy likely to prevent QUIN-induced neurotoxicity and KYN and 3-HAA–mediated immune suppression. Cancer Res; 72(22); 5649–57. ©2012 AACR.
Enabling a robust scalable manufacturing process for therapeutic exosomes through oncogenic immortalization of human ESC-derived MSCs (2011)

Our results demonstrated that MYC transformation is a practical strategy in ensuring an infinite supply of cells for the production of exosomes in the milligram range as either therapeutic agents or delivery vehicles. In addition, the increased proliferative rate by MYC transformation reduces the time for cell production and thereby reduces production costs.
Unsupervised Learning With Random Forest Predictors (2006)

A random forest (RF) predictor is an ensemble of individual tree predictors. As part of their construction, RF predictors naturally lead to a dissimilarity measure between the observations. One can also define an RF dissimilarity measure between unlabeled data: the idea is to construct an RF predictor that distinguishes the “observed” data from suitably generated synthetic data. The observed data are the original unlabeled data and the synthetic data are drawn from a reference distribution. Here we describe the properties of the RF dissimilarity and make recommendations on how to use it in practice.An RF dissimilarity can be attractive because it handles mixed variable types well, is invariant to monotonic transformations of the input variables, and is robust to outlying observations. The RF dissimilarity easily deals with a large number of variables due to its intrinsic variable selection; for example, the Addcl 1 RF dissimilarity weighs the contribution of each variable according to how dependent it is on other variables.We find that the RF dissimilarity is useful for detecting tumor sample clusters on the basis of tumor marker expressions. In this application, biologically meaningful clusters can often be described with simple thresholding rules.
Artificial Molecular Machines (2000)

The miniaturization of components used in the construction of working devices is being pursued currently by the large-downward (top-down) fabrication. This approach, however, which obliges solid-state physicists and electronic engineers to manipulate progressively smaller and smaller pieces of matter, has its intrinsic limitations. An alternative approach is a small-upward (bottom-up) one, starting from the smallest compositions of matter that have distinct shapes and unique properties-namely molecules. In the context of this particular challenge, chemists have been extending the concept of a macroscopic machine to the molecular level. A molecular-level machine can be defined as an assembly of a distinct number of molecular components that are designed to perform machinelike movements (output) as a result of an appropriate external stimulation (input). In common with their macroscopic counterparts, a molecular machine is characterized by 1) the kind of energy input supplied to make it work, 2) the nature of the movements of its component parts, 3) the way in which its operation can be monitored and controlled, 4) the ability to make it repeat its operation in a cyclic fashion, 5) the timescale needed to complete a full cycle of movements, and 6) the purpose of its operation. Undoubtedly, the best energy inputs to make molecular machines work are photons or electrons. Indeed, with appropriately chosen photochemically and electrochemically driven reactions, it is possible to design and synthesize molecular machines that do work. Moreover, the dramatic increase in our fundamental understanding of self-assembly and self-organizational processes in chemical synthesis has aided and abetted the construction of artificial molecular machines through the development of new methods of noncovalent synthesis and the emergence of supramolecular assistance to covalent synthesis as a uniquely powerful synthetic tool. The aim of this review is to present a unified view of the field of molecular machines by focusing on past achievements, present limitations, and future perspectives. After analyzing a few important examples of natural molecular machines, the most significant developments in the field of artificial molecular machines are highlighted. The systems reviewed include 1) chemical rotors, 2) photochemically and electrochemically induced molecular (conformational) rearrangements, and 3) chemically, photochemically, and electrochemically controllable (co-conformational) motions in interlocked molecules (catenanes and rotaxanes), as well as in coordination and supramolecular complexes, including pseudorotaxanes. Artificial molecular machines based on biomolecules and interfacing artificial molecular machines with surfaces and solid supports are amongst some of the cutting-edge topics featured in this review. The extension of the concept of a machine to the molecular level is of interest not only for the sake of basic research, but also for the growth of nanoscience and the subsequent development of nanotechnology.
Selective release of human adipocyte fatty acids according to molecular structure (1997)

The objective of the present study was to investigate the mobilization of individual fatty acids from human white fat cells. Mammary adipose tissue from eight healthy non-obese women in their normal dietary state was collected, and isolated adipocytes were incubated with lipolytic agents. The mobilization of 34 individual fatty acids was measured by comparing the composition of non-esterified fatty acids (NEFA) with that of the triacylglycerols (TAG) from which they originated through lipolysis. Compared with TAG, NEFA were enriched in some polyunsaturated fatty acids with 18-20 carbon atoms. Conversely, the percentage of very-long-chain (20-22 carbon atoms) saturated and monounsaturated fatty acids was approx. 2 times lower in NEFA than in TAG. The relative mobilization (% in NEFA/% in TAG) of the most readily mobilized fatty acid (C20:5, n-3; 2.25) was more than 6-fold higher than that of the least readily mobilized (C22:1,n-11; 0.37). Relationships were found between the molecular structure of fatty acids and their mobilization rate. For a given chain length, the relative mobilization rate increased with increasing unsaturation, whereas for a given unsaturation, it decreased with increasing chain length. The relative mobilization rate for essential fatty acids decreased in the following order: C20:5,n-3>C20:4,n-6>C18:3,n-3>C18:2, n-6>C22:6,n-3. Interestingly, C20:5,n-3 and C20:4,n-6, which are respectively precursors of the 3- and 2-series of prostaglandins, were preferentially mobilized. It is concluded that fatty acids are selectively mobilized from human fat cells according to molecular structure, in full agreement with animal studies. By modulating the qualitative fatty acid supply to organs and by remodelling the fatty acid composition of adipose tissue, this selectivity would be relevant for consideration in physiology, health and epidemiology.
Bulk-layout-compatible 0.18 μm SOI-CMOS technology using body-fixed partial trench isolation (PTI) (2003)

Transistor performance improvement has been strongly required for work toward highly integrated intelligent system LSIs. To meet this demand, silicon on insulator (SOI) has become of major interest for next generation devices, because it can offer durable device scaling as compared with bulk devices (Schepis et al. 1997). The critical issues for SOI are floating-body effects such as deterioration in drain current (Matsumoto et al. 1999), dynamic threshold voltage instability (Lu et al. 1997), and increased soft error rate (Wada et al. 1998). These have restricted the application of floating SOI, especially to analog circuits. Some circuit modifications and body contact insertions are necessary. A full body-fixing structure is another approach and some techniques have been proposed (Koh et al. 1997; Iwamatsu et al. 1995). However, when using these techniques, there have been some shortcomings in terms of scalability and layout compatibility. In this report, we propose a partial trench isolation (PTI) technique in which the body potential is fixed through the region under the trench oxide. With the PTI technology, we can eliminate floating-body effects while maintaining SOI-inherent merits and can realize scalable deep sub-quarter micron LSIs using accumulated bulk-design properties without layout modification. Moreover, the feasibility for ULSIs is demonstrated by a fully functional 4 Mbit SRAM.
Oral History and Autobiography: Some Observations Recording the Life Story of Dr Doreen Kartinyeri (2003)

Interview recording is often the first step in compiling life stories of Australian Aboriginal people for presentation in formats suitable for the public domain. But, with backgrounds in deeply flawed mission and 'welfare' approaches to education in the past, many have had little opportunity to develop experience and skills required in such complex enterprises, even when, as in this case, the subject is of considerable intellect and achievement; necessarily, work with collaborators from mainstream cultural and often academic backgrounds is usually required. This paper describes some aspects of the 'intersubjectivity' of such collaborations: there is potential tension between dependence in the practicalities of the process and personal independence of identity and voice; and some of the challenges and rewards arising from differences between subject and collaborator in life perspectives and approach are identified, aspects that require balance in the process.
Single-Nanoparticle Electrochemistry through Immobilization and Collision (2016)

Metal nanoparticles are key electrode materials in a variety of electrochemical applications including basic electron-transfer study, electrochemical sensing, and electrochemical surface enhanced Raman spectroscopy (SERS). Metal nanoparticles have also been extensively applied to electrocatalytic processes in recent years due to their high catalytic activity and large surface areas. Because the catalytic activity of metal nanoparticle is often highly dependent on their size, shape, surface ligands, and so forth, methods for examining and better understanding the correlation between particle structure and function are of great utility in the development of more efficient catalytic systems. Despite considerable progress in this field, the understanding of the structure-activity relationships remains challenging in nanoparticle-based electrochemistry and electrocatalysis due to limitations associated with traditional ensemble measurements. One of the major issues is the ensemble averaging of the electrocatalytic response which occurs over a very large number of nanoparticles of various sizes and shapes. Additionally, the electrochemical response can also be greatly affected by properties of the ensemble itself, such as the particle spacing. The ability to directly measure kinetics of electrochemical reactions at structurally well-characterized single nanoparticles opens up new possibilities in many important areas including nanoscale electrochemistry, electrochemical sensing, and nanoparticle electrocatalysis. When a macroscopic electrode is placed in a solution containing redox molecules and metal nanoparticles, random collision and adsorption of nanoparticles occurs at the electrode surface in addition to redox reactions when a suitable potential is present on the electrode. In a special case where particles are catalytically more active than the substrate, the faradaic signals can be greatly amplified on particle surfaces and a steady shift in the baseline current would be expected due to many particles adsorbing on the electrode. Single particle events can be temporally resolved when an ultramicroelectrode (UME) is used as the recording electrode. The use of an UME not only reduces the collision frequency, but also greatly decreases baseline noise, thereby resulting in clear resolution of single collision events. Single particle collision has quickly grown into a popular electroanalytical technique in recent years. Alternatively, one can use nanoelectrodes to immobilize single nanoparticles so that they can be individually studied in electrochemistry and electrocatalysis. Nanoparticle immobilization also allows one to obtain detailed structural information on the same particles and offers enormous potential for developing more comprehensive understanding of the structure-function relationship in nanoparticle-based electrocatalysts. This Account summarizes recent electrochemical experiments of single metal nanoparticles which have been performed by our group using both of these schemes.
Case 38-2012 (2012)

A 60-year-old man with abdominal pain had abdominal and thoracic aortic aneurysms suggestive of mycotic aneurysms. The abdominal aneurysm was resected. Cultures were negative; fever persisted. Six weeks later, chest pain developed and the thoracic aneurysm had enlarged.
Three mouse models of human thalassemia. (1981)

Three types of mice with globin gene mutations, called 352HB, 27HB, and Hbath-J, appear to be true animal models of human thalassemia. Expression of the alpha-globin genes in three stocks of mice, each one heterozygous for one of the alpha-globin mutations, was examined at the polypeptide, RNA, and DNA levels. alpha-Globin polypeptide chains, relative to beta-globin chains in heterozygous thalassemic mice, are present at approximately 80% of normal. The ratios of alpha-globin to beta-globin RNA sequences are also 75-80% of normal, exactly reflecting the alpha-globin to beta-globin chain ratios. In the case of mutant 352HB, at least one alpha-globin gene is deleted. Thalassemic mouse erythroid cells appear to compensate partially for the loss of half of their alpha-globin genes.
Regulation of the p85/p110 Phosphatidylinositol 3′-Kinase: Stabilization and Inhibition of the p110α Catalytic Subunit by the p85 Regulatory Subunit (1998)

We propose a novel model for the regulation of the p85/pl10alpha phosphatidylinositol 3'-kinase. In insect cells, the p110alpha catalytic subunit is active as a monomer but its activity is decreased by coexpression with the p85 regulatory subunit. Similarly, the lipid kinase activity of recombinant glutathione S-transferase (GST)-p110alpha is reduced by 65 to 85% upon in vitro reconstitution with p85. Incubation of p110alpha/p85 dimers with phosphotyrosyl peptides restored activity, but only to the level of monomeric p110alpha. These data show that the binding of phosphoproteins to the SH2 domains of p85 activates the p85/p110alpha dimers by inducing a transition from an inhibited to a disinhibited state. In contrast, monomeric p110 had little activity in HEK 293T cells, and its activity was increased 15- to 20-fold by coexpression with p85. However, this apparent requirement for p85 was eliminated by the addition of a bulky tag to the N terminus of p110alpha or by the growth of the HEK 293T cells at 30 degrees C. These nonspecific interventions mimicked the effects of p85 on p110alpha, suggesting that the regulatory subunit acts by stabilizing the overall conformation of the catalytic subunit rather than by inducing a specific activated conformation. This stabilization was directly demonstrated in metabolically labeled HEK 293T cells, in which p85 increased the half-life of p110. Furthermore, p85 protected p110 from thermal inactivation in vitro. Importantly, when we examined the effect of p85 on GST-p110alpha in mammalian cells at 30 degrees C, culture conditions that stabilize the catalytic subunit and that are similar to the conditions used for insect cells, we found that p85 inhibited p110alpha. Thus, we have experimentally distinguished two effects of p85 on p110alpha: conformational stabilization of the catalytic subunit and inhibition of its lipid kinase activity. Our data reconcile the apparent conflict between previous studies of insect versus mammalian cells and show that p110alpha is both stabilized and inhibited by dimerization with p85.
Tetrabenazine (Xenazine), An FDA-Approved Treatment Option For Huntington's Disease-Related Chorea. (2008)

Huntington’s disease (HD) is a progressive autosomal-dominant neurodegenerative disorder caused by 36 or more trinucleotide (CAG) repeats on the short arm of chromosome 4.1 The higher the number of repeats on the huntingtin gene, the more fully present the disorder. As a result of this abnormality, mutated huntingtin protein is formed and is a hallmark of HD.

HD occurs worldwide in all ethnic groups but predominantly in Caucasian populations.1 The prevalence rate in Europe and the U.S. is 4 to 8 per 100,000 individuals.2 In Japan, the prevalence is only 10% of this number.2

Symptoms generally appear between the ages of 35 and 40 but have been recorded as early as five years of age. These symptoms are devastating and disabling and involve movement disorders, incoordination, cognitive decline, personality and behavioral changes.1,2 The most striking and characteristic symptom is chorea, or involuntary dance-like movements that seem purposeless and abrupt. As the severity of symptoms progresses, patients are at a higher risk of dying because of complications, such as falls and aspiration. The typical period between diagnosis and death of the patient is 20 years.3

As of this writing, no treatment is available that can delay the progression of HD. Existing management strategies focus on improving symptoms and quality of life.4 Neuroleptic agents, including dopamine receptor blockers and presynaptic dopamine-depleting agents, have been used to control choreic movements.2

Until now, no medication had been approved in the U.S. for the treatment of chorea or any other symptom associated with HD. In August 2008, the FDA approved tetrabenazine (Xenazine) for this indication. In September 2008, Ovation Pharmaceuticals acquired the exclusive license in the U. S. to market this orphan drug from Prestwick Pharmaceuticals.

Tetrabenazine has been used for decades in several countries to treat chorea and other hyperkinetic movement disorders, such as dystonias and tics.5 This article provides a concise review of the pharmacology, pharmacokinetics, safety, and efficacy of this much needed treatment option to ameliorate some of the disabling symptoms of HD.