gebhart/patrepeval huggingface dataset:
A Scalable System for Production of Functional Pancreatic Progenitors from Human Embryonic Stem Cells (2012)

Development of a human embryonic stem cell (hESC)-based therapy for type 1 diabetes will require the translation of proof-of-principle concepts into a scalable, controlled, and regulated cell manufacturing process. We have previously demonstrated that hESC can be directed to differentiate into pancreatic progenitors that mature into functional glucose-responsive, insulin-secreting cells in vivo. In this study we describe hESC expansion and banking methods and a suspension-based differentiation system, which together underpin an integrated scalable manufacturing process for producing pancreatic progenitors. This system has been optimized for the CyT49 cell line. Accordingly, qualified large-scale single-cell master and working cGMP cell banks of CyT49 have been generated to provide a virtually unlimited starting resource for manufacturing. Upon thaw from these banks, we expanded CyT49 for two weeks in an adherent culture format that achieves 50-100 fold expansion per week. Undifferentiated CyT49 were then aggregated into clusters in dynamic rotational suspension culture, followed by differentiation en masse for two weeks with a four-stage protocol. Numerous scaled differentiation runs generated reproducible and defined population compositions highly enriched for pancreatic cell lineages, as shown by examining mRNA expression at each stage of differentiation and flow cytometry of the final population. Islet-like tissue containing glucose-responsive, insulin-secreting cells was generated upon implantation into mice. By four- to five-months post-engraftment, mature neo-pancreatic tissue was sufficient to protect against streptozotocin (STZ)-induced hyperglycemia. In summary, we have developed a tractable manufacturing process for the generation of functional pancreatic progenitors from hESC on a scale amenable to clinical entry.
Diagnostic and therapeutic injection of the hip and knee. (2003)

Joint injection of the hip and knee regions is a useful diagnostic and therapeutic tool for the family physician. In this article, the injection procedure for the greater trochanteric bursa, the knee joint, the pes anserine bursa, the iliotibial band, and the prepatellar bursa is reviewed. Indications for greater trochanteric bursa injection include acute and chronic inflammation associated with osteoarthritis, rheumatoid arthritis, repetitive use, and other traumatic injuries to the area. For the knee joint, aspiration may be performed to aid in the diagnosis of an unexplained effusion and relieve discomfort caused by an effusion. Injection of the knee can be performed for viscosupplementation or corticosteroid therapy. Indications for corticosteroid injection include advanced osteoarthritis and other inflammatory arthritides, such as gout or calcium pyrophosphate deposition disease. Swelling and tenderness of pes anserine or prepatellar bursae can be relieved with aspiration and corticosteroid injection. Persistent pain and disability from iliotibial band syndrome respond to local injection therapy. The proper technique, choice and quantity of pharmaceuticals, and appropriate follow-up are essential for effective outcomes.
The Effect of Hypothermia on Transient Middle Cerebral Artery Occlusion in the Rat (1992)

We investigated the effect of moderate whole body hypothermia (30 degrees C) on transient middle cerebral artery occlusion (MCAO) in the rat. Male Wistar rats were subjected to 2 h of ischemia by inserting a suture into the lumen of the internal carotid artery and occluding the origin of the MCA. Experimental groups were (a) MCAO induced at 37 degrees C body temperature (n = 15); (b) 30 degrees C body temperature induced prior to ischemia and maintained for 2 h of MCAO and 1 h of reperfusion (n = 12); and (c) MCAO with regional brain and body temperatures measured in normothermic (n = 3) and hypothermic MCAO rats (n = 2). Histopathological evaluation was performed 96 h after reperfusion. All normothermic MCAO animals exhibited ischemic infarct involving the ipsilateral cortex and basal ganglia with infiltration of neutrophils, macrophages, and microvascular proliferation. Hypothermic MCAO animals exhibited minor ischemic damage ranging from selective neuronal injury to small focal areas of infarct with minimal inflammatory response. Our data demonstrate that transient ischemia induced by using the intra-arterial suture method to occlude the MCA results in a reproducible brain lesion and that moderate hypothermia has a profound protective effect on the brain injury after transient MCAO.
Increased risk of deep-vein thrombosis in patients with multiple myeloma receiving thalidomide and chemotherapy (2001)

The occurrence of deep-vein thrombosis (DVT) in patients with newly diagnosed multiple myeloma, who were randomly assigned to receive identical induction chemotherapy with or without thalidomide, are reported in this study. The 2 study arms were comparable with respect to key myeloma prognostic factors and known risk factors for DVT. One hundred patients received induction chemotherapy including 4 cycles of continuous infusion of combinations of dexamethasone, vincristine, doxorubicin, cyclophosphamide, etoposide, and cisplatin, and each patient completed at least one induction cycle. DVT developed in 14 of 50 patients (28%) randomly assigned to receive thalidomide but in only 2 of 50 patients (4%) not given the agent (P =.002). All episodes of DVT occurred during the first 3 cycles of induction. Administration of thalidomide was resumed safely in 75% of patients receiving anticoagulation therapy. Thus, thalidomide given in combination with multiagent chemotherapy and dexamethasone is associated with a significantly increased risk of DVT, which appears to be safely treated with anticoagulation and does not necessarily warrant discontinuation of thalidomide.
Characterization of a nitrogen-fixation (nif) gene cluster from Anabaena azollae 1a shows that closely related cyanobacteria have highly variable but structured intergenic regions (1995)

The exact identity of cyanobacteria that have been cultured from symbiotic associations with the water fern Azolla spp., whether they are required in the symbiotic process, and their relationship to the symbiotic species, is a matter of some debate. We have characterized a 6 kb region containing the nifB operon and the nifH gene from cyanobacterium Anabaena azollae 1a, a putative symbiont of Azolla caroliniana. Five complete open reading frames have been sequenced. All are very highly conserved when compared with the corresponding regions of Anabaena sp. PCC 7120, with 93% to 97% identity at the nucleotide level and 93% to almost 100% at the amino-acid level. The intergenic regions, however, are not highly conserved (53-89% identity) when compared to the corresponding regions of Anabaena 7120: the A. azollae genome contains both more copies and more types of short tandemly repeated repetitive sequences than Anabaena 7120. The start points of transcription for both the nifB and nifH operons were mapped and found to be the same as those in Anabaena 7120. It was not possible to discern an improved consensus nif promoter sequence, but it was possible to define the likely extent of the promoter to within 40 bases upstream of the transcription start-point.
827. Potential anti-purines. Part II. The synthesis of 6- and 9-substituted purines and 8-azapurines (1958)

C. L. Leese and G. M. Timmis, J. Chem. Soc., 1958, 4107 DOI: 10.1039/JR9580004107
Robot feedback control based on stereo vision: towards calibration-free hand-eye coordination (2002)

This article describes the theory and implementation of a system that positions a robot manipulator using visual information from two cameras. The system simultaneously tracks the robot end-effector and visual features used to define goal positions. An error signal based on the visual distance between the end-effector and the target as defined and a control law that moves the robot to drive this error to zero is derived. The control law has been integrated into a system that performs tracking and stereo control on a single processor with no special purpose hardware at real-time rates. Experiments with the system have shown that the controller is so robust to calibration error that the cameras can be moved several centimeters and rotated several degrees while the system is running with no adverse effects.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
IL-10 Inhibits Inflammation and Attenuates Left Ventricular Remodeling After Myocardial Infarction via Activation of STAT3 and Suppression of HuR (2008)

Persistent inflammatory response has adverse effects on left ventricular (LV) function and remodeling following acute myocardial infarction. We hypothesized that suppression of inflammation with interleukin (IL)-10 treatment attenuates LV dysfunction and remodeling after acute myocardial infarction. After the induction of acute myocardial infarction, mice were treated with either saline or recombinant IL-10, and inflammatory response and LV functional and structural remodeling changes were evaluated. IL-10 significantly suppressed infiltration of inflammatory cells and expression of proinflammatory cytokines in the myocardium. These changes were associated with IL-10-mediated inhibition of p38 mitogen-activated protein kinase activation and repression of the cytokine mRNA-stabilizing protein HuR. IL-10 treatment significantly improved LV functions, reduced infarct size, and attenuated infarct wall thinning. Myocardial infarction-induced increase in matrix metalloproteinase (MMP)-9 expression and activity was associated with increased fibrosis, whereas IL-10 treatment reduced both MMP-9 activity and fibrosis. Small interfering RNA knockdown of HuR mimicked IL-10-mediated reduction in MMP-9 expression and activity in NIH3T3 cells. Moreover, IL-10 treatment significantly increased capillary density in the infarcted myocardium which was associated with enhanced STAT3 phosphorylation. Taken together, our studies demonstrate that IL-10 suppresses inflammatory response and contributes to improved LV function and remodeling by inhibiting fibrosis via suppression of HuR/MMP-9 and by enhancing capillary density through activation of STAT3.
Increased Life-Span of age -1 Mutants in Caenorhabditis elegans and Lower Gompertz Rate of Aging (1990)

A mutation in the age-1 gene of the nematode Caenorhabditis elegans has been shown to result in a 65 percent increase in mean life-span and a 110 percent increase in maximum life-span at 25 degrees. One of the hallmarks of organismic aging and senescent processes is an exponential acceleration of age-specific mortality rate with chronological age. This exponential acceleration is under genetic control: age-1 mutant hermaphrodites show a 50 percent slower rate of acceleration of mortality with chronological age than wild-type strains. Mutant males also show a lengthening of life and a slowing of the rate of acceleration of mortality, although age-1 mutant males still have significantly shorter life-spans than do hermaphrodites of the same genotype. The slower rates of acceleration of mortality are recessive characteristics of the age-1 mutant alleles examined.
Alternative splicing in concert with protein intrinsic disorder enables increased functional diversity in multicellular organisms (2006)

Alternative splicing of pre-mRNA generates two or more protein isoforms from a single gene, thereby contributing to protein diversity. Despite intensive efforts, an understanding of the protein structure-function implications of alternative splicing is still lacking. Intrinsic disorder, which is a lack of equilibrium 3D structure under physiological conditions, may provide this understanding. Intrinsic disorder is a common phenomenon, particularly in multicellular eukaryotes, and is responsible for important protein functions including regulation and signaling. We hypothesize that polypeptide segments affected by alternative splicing are most often intrinsically disordered such that alternative splicing enables functional and regulatory diversity while avoiding structural complications. We analyzed a set of 46 differentially spliced genes encoding experimentally characterized human proteins containing both structured and intrinsically disordered amino acid segments. We show that 81% of 75 alternatively spliced fragments in these proteins were associated with fully (57%) or partially (24%) disordered protein regions. Regions affected by alternative splicing were significantly biased toward encoding disordered residues, with a vanishingly small P value. A larger data set composed of 558 SwissProt proteins with known isoforms produced by 1,266 alternatively spliced fragments was characterized by applying the pondr vsl1 disorder predictor. Results from prediction data are consistent with those obtained from experimental data, further supporting the proposed hypothesis. Associating alternative splicing with protein disorder enables the time- and tissue-specific modulation of protein function needed for cell differentiation and the evolution of multicellular organisms.
The Genetics of Crohn's Disease (2009)

From epidemiological data, based on concordance data in family studies, via linkage analysis to genome-wide association studies, we and others have accumulated robust evidence implicating more than 30 distinct genomic loci involved in the genetic susceptibility to Crohn's disease (CD). These loci encode genes involved in a number of homeostatic mechanisms: innate pattern recognition receptors (NOD2/CARD15, TLR4, CARD9), the differentiation of Th17-lymphocytes (IL-23R, JAK2, STAT3, CCR6, ICOSLG), autophagy (ATG16L1, IRGM, LRRK2), maintenance of epithelial barrier integrity (IBD5, DLG5, PTGER4, ITLN1, DMBT1, XBP1), and the orchestration of the secondary immune response (HLA-region, TNFSF15/TL1A, IRF5, PTPN2, PTPN22, NKX2-3, IL-12B, IL-18RAP, MST1). While many of these loci also predispose to pediatric CD, an additional number of childhood-onset loci have been identified recently (e.g., TNFRSF6B). Not only has the identification of these loci improved our understanding of the pathophysiology of CD, this knowledge also holds real promise for clinical practice.
Treatment of Leptomeningeal Metastasis With Intraventricular Administration of Depot Cytarabine (DTC 101) (1993)

Depo cytarabine (DTC 101 [formerly identified as Depo/Ara-C]) is a slow-releasing, depot formulation in which cytarabine is encapsulated within the aqueous compartments of microscopic (DepoFoam) particles. A phase I trial of DTC 101, given intraventricularly, was conducted in patients with leptomeningeal metastasis. Nine patients were given 1 to 7 cycles of DTC 101 in doses ranging from 25 to 125 mg that were administered via an Ommaya reservoir into the lateral ventricle. The dose-limiting toxic reaction was encephalopathy that occurred at the 125-mg dose level. All toxic episodes but one were transient and reversible, with the total duration of toxicity lasting from 1 to 7 days. The ventricular concentration of free cytarabine released from DTC 101 into cerebrospinal fluid decreased biexponentially with an initial half-life of 7.2 +/- 1.7 (+/- SEM) hours and a terminal half-life of 140 +/- 49 hours. The cerebrospinal fluid was cleared of malignant cells within 3 weeks of initial therapy in five of six cytologically evaluable patients. The duration of response ranged from 2 to more than 14 weeks, with a median of over 11 weeks. In conclusion, DTC 101 appears to be a pharmacologically attractive agent for use against leptomeningeal metastasis. The toxic episodes that occur with this therapy are well tolerated by patients.
Amplification/Overexpression of a Mitotic Kinase Gene in Human Bladder Cancer (2002)

STK15 gene amplification and associated increased expression of the mitotic kinase it encodes are associated with aneuploidy and aggressive clinical behavior in human bladder cancer.
Molecular Characterization of the Maize Rp1-D Rust Resistance Haplotype and Its Mutants (1999)

The Rp1-D gene for resistance to maize common rust (Puccinia sorghi) is a member of a complex locus (haplotype) composed of Rp1-D and approximately eight other gene homologs. The identity of Rp1-D was demonstrated by using two independent gene-tagging approaches with the transposons Mutator and Dissociation. PIC20, a disease resistance (R) gene analog probe previously mapped to the rp1 locus, detected insertion of Dissociation in an Rp1-D mutation and excision in three revertants. Independent libraries probed with the PIC20 or Mutator probes resulted in isolation of the same gene sequence. Rp1-D belongs to the nucleotide binding site, leucine-rich repeat class of R genes. However, unlike the rust resistance genes M and L6 from flax, the maize Rp1-D gene does not encode an N-terminal domain with similarity to the signal transduction domains of the Drosophila Toll protein and mammalian interleukin-1 receptor. Although the abundance of transcripts of genes from the rp1 complex changed with leaf age, there was no evidence of any change due to inoculation with avirulent or virulent rust biotypes. A set of 27 Rp1-D mutants displayed at least nine different deletions of Rp1-D gene family members that were consistent with unequal crossing-over events. One mutation (Rp1-D*-24) resulted in deletion of all but one gene family member. Other unique deletions were observed in the disease lesion mimic Rp1-D*-21 and the partially susceptible mutant Rp1-D*-5. Different rp1 specificities have distinct DNA fingerprints (haplotypes). Analysis of recombinants between rp1 specificities indicated that recombination had occurred within the rp1 gene complex. Similar analyses indicated that the rust R genes at the rp5 locus, 2 centimorgans distal to rp1, are not closely related to Rp1-D.
Object-oriented design and programming (1997)

An undergraduate junior or senior level course in object-oriented design and programming is described. The course assumes familiarity with ANSI C and with data structures. The course is a popular elective among upper division students. The small, elegant, pure, and powerful object-oriented language Eiffel is used to illustrate the significant object concepts and as a guide to identifying the most relevant subsets of the C++ and Java languages.
Structural Studies of Allelic Diversity of the MHC Class I Homolog MIC-B, a Stress-Inducible Ligand for the Activating Immunoreceptor NKG2D (2002)

MIC-A and MIC-B are distant MHC class I homologs that serve as stress-inducible Ags on epithelial and epithelially derived cells. They are ligands for the widely expressed activating immunoreceptor NKG2D. To define the structural and functional consequences of sequence differences between MIC-A and MIC-B and between alleles of MIC-A and alleles of MIC-B, we determined the crystal structure of one allele of human MIC-B. Comparisons between the two previously reported MIC-A crystal structures and the MIC-B crystal structure show that, as expected, MIC-B is very similar in structure to MIC-A and likely interacts with NKG2D in an analogous manner. The interdomain flexibility observed in the MIC-A structures, a feature unique to MIC proteins among MHC class I proteins and homologs, is also displayed by MIC-B, with an interdomain relationship intermediate between the two examples of MIC-A structures. Mapping sequence variations onto the structures of MIC-A and MIC-B reveals patterns completely distinct from those displayed by classical MHC class I proteins, with a number of substitutions falling on positions likely to affect interactions with NKG2D, but with other positions lying distant from the NKG2D binding sites or buried within the core of the proteins.
部署ISA Server 2006企业版防火墙阵列 (2007)

我在以前的多期杂志中连续讲解了微软ISA2004的安装、初试和企业部署方案．对ISA2004的部分特性作了讲解和演示，相信很多朋友已经对ISA2004不再陌生，或者已经在自己的企业中应用。不过以前讲解的内容基本没有涉及到ISA2004企业版的应用，为了弥补不足，这次我将继续带领大家来感受ISA2006企业版防火墙阵列部署．将会更深入的了解ISA防火墙在企业中的实用价值。
Transrenal Ureteral Occlusion with Gianturco Coils and Gelatin Sponge (1989)

The authors report the use of Gianturco coils and gelatin sponge plugs to achieve complete occlusion of nine ureters in five patients with advanced pelvic malignancies and lower urinary tract fistulas. The method is simple to apply, is readily available, and to date has been associated with no significant complications. These results suggest that, before more elaborate methods of ureteral occlusion are applied, the use of coils and gelatin sponge should be considered as the primary method of ureteral occlusion. Further work is needed to elaborate the exact mechanism by which these materials cause occlusion.
High-Affinity Peptide Nucleic Acid Oligomers Containing Tricyclic Cytosine Analogues (2002)

[structure: see text] Peptide nucleic acid (PNA) monomers containing the tricyclic cytosine analogues phenoxazine, 9-(2-aminoethoxy)phenoxazine (G-clamp), and 9-(3-aminopropoxy)phenoxazine (propyl-G-clamp) have been synthesized. The modified nucleobases were incorporated into PNA oligomers using Boc-chemistry for solid-phase synthesis. PNAs containing single G-clamp modifications exhibit significantly enhanced affinity toward RNA and DNA targets relative to unmodified PNA while maintaining mismatch discrimination. These PNA G-clamp modifications exhibit the highest increase in affinity toward nucleic acid targets reported so far for PNA modifications.
Differential display and cloning of messenger RNAs from human breast cancer versus mammary epithelial cells. (1992)

Identification of the genes that are specifically expressed in tumor cells but not in normal cells (oncogenes), or vice versa (tumor suppressor genes), is important for understanding the molecular basis of cancer. The differential display technique was applied to compare mRNAs from normal and tumor-derived human mammary epithelial cells, cultured under the same conditions. Complementary DNA fragments corresponding to several apparently differentially expressed mRNAs were recovered and sequenced. They exhibit characteristics of the 3' end of eukaryotic mRNA, as predicted by the method. A complementary DNA fragment seen only in the normal cell was used as a probe to isolate its corresponding complementary DNA clone from a library. Northern analysis confirmed its differential expression. Thus, this method can be used for detecting, cloning, and sequencing of genes that are unique to a host of biological and disease processes.
Gradient Feature Selection for Online Boosting (2007)

Boosting has been widely applied in computer vision, especially after Viola and Jones's seminal work. The marriage of rectangular features and integral-image- enabled fast computation makes boosting attractive for many vision applications. However, this popular way of applying boosting normally employs an exhaustive feature selection scheme from a very large hypothesis pool, which results in a less-efficient learning process. Furthermore, this poses additional constraint on applying boosting in an onine fashion, where feature re-selection is often necessary because of varying data characteristic, but yet impractical due to the huge hypothesis pool. This paper proposes a gradient-based feature selection approach. Assuming a generally trained feature set and labeled samples are given, our approach iteratively updates each feature using the gradient descent, by minimizing the weighted least square error between the estimated feature response and the true label. In addition, we integrate the gradient-based feature selection with an online boosting framework. This new online boosting algorithm not only provides an efficient way of updating the discriminative feature set, but also presents a unified objective for both feature selection and weak classifier updating. Experiments on the person detection and tracking applications demonstrate the effectiveness of our proposal.