gebhart/patrepeval huggingface dataset:
The potential mechanism of the diabetogenic action of streptozotocin: inhibition of pancreatic β-cell O-GlcNAc-selective N-acetyl-β-d-glucosaminidase (2001)

Streptozotocin (STZ), an analogue of GlcNAc, inhibits purified rat spleen O-GlcNAc-selective N-acetyl-β-d-glucosaminidase (O-GlcNAcase), the enzyme that removes O-GlcNAc from protein. We have shown previously that STZ increases pancreatic islet O-linked protein glycosylation. In light of these data, we investigated the possibility further that STZ causes β-cell death by inhibiting O-GlcNAcase. In isolated islets, the time course and dose curve of STZ-induced O-glycosylation correlated with β-cell toxicity. STZ inhibition of rat islet O-GlcNAcase activity also paralleled that of its β-cell toxicity, with significant inhibition occurring at a concentration of 1mM. In contrast, STZ inhibition of rat brain O-GlcNAcase and β-TC3 insulinoma cell O-GlcNAcase was significantly right-shifted compared with islets, with STZ only significantly inhibiting activity at a concentration of 5mM, the same concentration required for β-TC3 cell toxicity. In comparison, N-methyl-N-nitrosourea, the nitric oxide-donating portion of STZ, did not cause increased islet O-glycosylation, β-cell toxicity or inhibition of β-cell O-GlcNAcase. Enhanced STZ sensitivity of islet O-GlcNAcase compared with O-GlcNAcase from other tissues or an insulinoma cell line suggests why actual islet β-cells are particularly sensitive to STZ. Confirming this idea, STZ-induced islet β-cell toxicity was completely blocked by GlcNAc, which also prevented STZ-induced O-GlcNAcase inhibition, but was not even partially blocked by glucose, glucosamine or GalNAc. Together, these data demonstrate that STZ's inhibition of β-cell O-GlcNAcase is the mechanism that accounts for its diabetogenic toxicity.
A cis-acting element in the 3'-untranslated region of human TNF-alpha mRNA renders splicing dependent on the activation of protein kinase PKR (1999)

We report a role for the 3'-untranslated region in control of mRNA splicing and show that human TNF-alpha 3' UTR harbors a cis-acting element that renders splicing of precursor transcripts dependent on activation of PKR, the RNA-activated protein kinase that phosphorylates eukaryotic initiation factor 2 (eIF2). When this element, designated 2-APRE, is present, splicing becomes sensitive to inhibition by the PKR inhibitor, 2-aminopurine, or by coexpression of transdominant-negative mutant PKR. Our results reveal that activation of PKR is required for splicing of mRNA when precursor transcripts contain the 2-APRE and that increased expression of wild-type PKR enhances their splicing efficiency. Thus, PKR responds as trans-acting factor to the 2-APRE. 2-APRE RNA forms a stable, 17-bp stem-loop structure and strongly activates PKR in vitro, inducing eIF2alpha phosphorylation. Despite its ability to activate PKR during splicing, the 2-APRE within the 3' UTR does not affect translation efficiency of the resulting TNF-alpha mRNA in transfected cells. PKR and the 3' UTR thus interact during mRNA splicing to confer a novel type of regulation on expression of the TNF-alpha gene.
Construction of a matrix-matrix crossbar optical interconnect employing diffractive fan-out and fan-in elements (1993)

An optical cross-bar interconnect incorporating diffractive/holographic optics and capable of providing high-bandwidth fully non-blocking links between 64 independent electronic processors is the goal of the authors project: 'Optically Connected Parallel Machines'. To test a number of new concepts a prototype 16*16 interconnect has been assembled as a first step. The optical arrangement of the prototype 16*16 crossbar interconnect that has been constructed is shown in figure 2. The input channels correspond to single-mode fibres configured as a two-dimensional array, while, to ensure efficient fan-in of multiple incoherent light beams, the output fibres, which are again configured as a square array, are multimode. A polarising beam splitter is used to separate the signals returning from the reflective SLM and direct them towards the output. The optical elements used to implement the required fan-out and fan-in functions, are discussed.
A multimodal fNIRS and EEG-based BCI study on motor imagery and passive movement (2013)

In EEG-based motor imagery Brain-Computer interface (BCI), EEG data collected in the calibration phase is used as a subject-specific model to classify the EEG data in the evaluation phase. Previous study has shown the feasibility of calibrating EEG-based BCI from passive movement. This paper investigates the primary sensorimotor area activation from fNIRS on 4 subjects using multimodal NIRS and EEG-based BCI system while performing motor imagery and passive movement of the hand by a Haptic Knob robot. NIRS_SPM is used to compute the changes in hemoglobin response and to generate brain activation map based on the contrasts of motor imagery versus idle and passive movement versus idle. The results on the contrasts showed that passive movement versus idle yielded significant differences compared to motor imagery versus idle. In addition, the results of classifying the NIRS and EEG data separately also showed that the accuracies on classifying passive movement versus idle are better than that of motor imagery versus idle. The results suggest a potential of using passive movement data to calibrate motor imagery in a multimodal NIRS and EEG-based BCI.
Fenestrated Occluders for Treatment of ASD in Elderly Patients with Pulmonary Hypertension and/or Right Heart Failure (2007)

Atrial septal defect (ASD) occlusion in adult patients with advanced age and left or right heart diastolic or systolic heart failure and in patients with pulmonary arterial hypertension bears a considerable risk of deterioration of heart failure. Therefore, we conducted this feasibility trial in 15 ASD patients with pulmonary hypertension and/or right heart failure using a fenestrated Amplatzer septal occluder (AGA Medical Corporation, Golden Valley, MN), allowing an overflow of blood in both directions in case of univentricular diastolic or systolic heart failure. In all patients, the device could be implanted without complications. All symptomatic patients showed an improvement in the New York Heart Association (NYHA) class, and no right or left heart decompensation occurred. On echocardiography, right ventricular end diastolic dimension (RVEDD) and pulmonary artery pressure (PAP) decreased significantly, whereas left ventricular end diastolic dimension (LVEDD) increased. Our series of 15 patients with fenestrated ASD occlusion shows that high-risk ASD occlusion can safely be accomplished with excellent clinical results and without complications by a fenestrated occluder.
IL-1 is required for tumor invasiveness and angiogenesis (2003)

Here, we describe that microenvironmental IL-1 beta and, to a lesser extent, IL-1 alpha are required for in vivo angiogenesis and invasiveness of different tumor cells. In IL-1 beta knockout (KO) mice, local tumor or lung metastases of B16 melanoma cells were not observed compared with WT mice. Angiogenesis was assessed by the recruitment of blood vessel networks into Matrigel plugs containing B16 melanoma cells; vascularization of the plugs was present in WT mice, but was absent in IL-1 beta KO mice. The addition of exogenous IL-1 into B16-containing Matrigel plugs in IL-1 beta KO mice partially restored the angiogenic response. Moreover, the incorporation of IL-1 receptor antagonist to B16-containing plugs in WT mice inhibited the ingrowth of blood vessel networks into Matrigel plugs. In IL-1 alpha KO mice, local tumor development and induction of an angiogenic response in Matrigel plugs was less pronounced than in WT mice, but significantly higher than in IL-1 beta KO mice. These effects of host-derived IL-1 alpha and IL-1 beta were not restricted to the melanoma model, but were also observed in DA/3 mammary and prostate cancer cell models. In addition to the in vivo findings, IL-1 contributed to the production of vascular endothelial cell growth factor and tumor necrosis factor in cocultures of peritoneal macrophages and tumor cells. Host-derived IL-1 seems to control tumor angiogenesis and invasiveness. Furthermore, the anti-angiogenic effects of IL-1 receptor antagonist, shown here, suggest a possible therapeutic role in cancer, in addition to its current use in rheumatoid arthritis.
Trigonal scaffolds for multivalent targeting of melanocortin receptors (2014)

Melanocortin receptors can be used as biomarkers to detect and possibly treat melanoma. To these ends, molecules bearing one, two, or three copies of the weakly binding ligand MSH(4) were attached to scaffolds based on phloroglucinol, tripropargylamine, and 1,4,7-triazacyclononane by means of the copper-assisted azide-alkyne cyclization. This synthetic design allows rapid assembly of multivalent molecules. The bioactivities of these compounds were evaluated using a competitive binding assay that employed human embryonic kidney cells engineered to overexpress the melanocortin 4 receptor. The divalent molecules exhibited 10- to 30-fold higher levels of inhibition when compared to the corresponding monovalent molecules, consistent with divalent binding. The trivalent molecules were only statistically (∼2-fold) better than the divalent molecules, still consistent with divalent binding but inconsistent with trivalent binding. Possible reasons for these behaviors and planned refinements of the multivalent constructs targeting melanocortin receptors based on these scaffolds are discussed.
Treatment of basilar invagination by atlantoaxial joint distraction and direct lateral mass fixation (2004)

Joint distraction and firm lateral mass fixation in selected cases of basilar invagination is a reasonable surgical treatment for reducing the basilar invagination, restoring craniospinal alignment, and establishing fixation of the atlantoaxial joint.
Biopharmaceutical Drug Design and Development (1999)

New discoveries in biology are occurring at an incredible rate, and with these discoveries arise nearly unimaginable opportunities in every area of human existence. Imagine the excitement surround ing
Self-Assembled 1-Octadecanethiol Monolayers on Graphene for Mercury Detection (2010)

We report studies on surface modification of graphene with 1-octadecanethiol and its application as heavy metal sensors. The alkanethiol molecules can self-assemble into large-scale highly ordered monolayers on single-layer graphene regardless of the roughness of graphene surfaces inherited from the underlying amorphorous silicon oxide (SiO2) dielectric substrates. Atomically resolved scanning tunneling microscopy imaging of modified graphene sheets on SiO2 was conducted to reveal configuration details of the self-assembled structure. Functionalization of graphene field effect transistors (Gra-FETs) with 1-octadecanethiol was realized and successfully explored for mercury(II) (Hg2+) detection at 10 ppm.
Pathological prognostic factors in breast cancer. III. Vascular invasion: relationship with recurrence and survival in a large study with long‐term follow‐up (1994)

The invasion of vascular spaces (lymphatic and/or blood vessel) by tumour, as assessed on routine haematoxylin and eosin sections, was investigated in a consecutive series of 1704 women with primary operable invasive breast carcinoma. Strict morphological criteria were used. Patients were under 70 years of age and received definitive surgery with no adjuvant systemic therapies. Information from regular follow-up (range 3-17 years) was recorded on to a computer database. Definite vascular invasion was seen in 22.8% of cases and concurrence between pathologists was high. In univariate analyses, vascular invasion was strongly associated with lymph node stage (P < 0.0001), tumour size (P < 0.0001), histological grade (P < 0.0001) and type of tumour (P < 0.0001). In multivariate analyses vascular invasion was of independent prognostic significance for both survival and for local recurrence of tumour; patients with tumours showing no vascular invasion had a significant survival advantage and a reduced risk of local recurrence. No association with oestrogen receptor status or menopause status was seen. The results confirm that histological assessment of vascular invasion provides independent prognostic information in primary operable breast carcinoma which may be helpful in making clinical decisions.
Basal-cell keratins in cervical reserve cells and a comparison to their expression in cervical intraepithelial neoplasia. (1992)

Expression of keratins 5, 14 and 17 in endocervical subcolumnar reserve cells was detected by means of immunohistochemical studies using polypeptide specific monoclonal antibodies. These particular keratins that were found among others in basal cells could also be detected to a variable extent in metaplastic and dysplastic cervical lesions. In some cases of immature squamous metaplasia all three keratin subtypes were expressed throughout the full thickness of the epithelium. In contrast, in mature squamous metaplasia a compartmentalization of these keratins was observed. Mature squamous metaplastic epithelium showed a keratin distribution pattern comparable to ectocervical squamous epithelium, with the exception of keratin 17, which was only sporadically found in the basal layer of ectocervical epithelium and was always present in the basal cells of mature squamous metaplastic epithelium. During progression of cervical intraepithelial neoplasia a clear increase in the expression of keratin 17 was observed. However, also keratins 5 and 14 were expressed. Our results demonstrate that a considerable number of premalignant lesions of the uterine cervix express the same keratins as found in the progenitor reserve cells. Lesions that lack expression of keratin 17 may form a distinct group, which are regressive in nature and do not progress into cervical cancer.
COMPARATIVE PHARMACOKINETICS OF d‐ AND l‐ALPHAMETHYLDOPA IN PLASMA, AQUEOUS HUMOR, AND CEREBROSPINAL FLUID IN RABBITS (1988)

The 2 stereoisomers of alphamethyldopa (alpha MD) were separately injected IV at 3 different doses (3, 10, 30 mg/kg) in anesthetized rabbits. Samples of plasma, aqueous humor (AH), and cerebrospinal fluid (CSF) were collected over a 300-min period. The concentration of the aminoacid (AA) was determined by liquid chromatography and electrochemical detection. Parameters obtained from kinetic analyses of the plasma concentrations were close to the values reported in other species. Linear elimination kinetics were observed in the dose range studied. A marked dose-dependent entry of alpha MD was observed in AH. A stereospecific active transport of alpha MD was evidenced in the AH since the concentration of the L-isomer reached values above the plasma levels. CSF entry of the AA was small when compared to AH kinetics. A limited passive diffusion of the AA in the brain could account for this phenomenon. However, greater availability of the L-stereoisomer was still observed in CSF. These alpha MD kinetic analyses illustrate the adaptation of AH and CSF removal procedures to the pharmacokinetic studies of the brain and ocular entry of AA isomers.
Quadpartite Will Redux: Coping With the Effects of Decoupling (2005)

In a decoupled state with a smaller exemption, full use of the federal estate tax exemption in the first decedent's estate will result in state death tax being due upon the first decedent's death (a result of the smaller state exemption). Conversely, if use of the federal estate tax exemption is limited in the decedent's estate to the (smaller) state exemption, then more federal (if not state) estate tax will likely be due upon the death of the surviving spouse. Limiting use of the exemption in the first estate will increase the federal estate tax marital deduction for that decedent, and property qualifying for a marital deduction in the first decedent's estate will usually be included in the federal taxable estate of the surviving spouse.
T cell development in TCR- alpha beta transgenic mice. Analysis using V(D)J recombination substrates. (1995)

The major pathway of intrathymic T cell differentiation leads CD4-8- (DN) T lineage-committed precursors to TCR-alpha beta+ CD4+8- or CD4-84+ (SP) T lymphocytes. The expression of functionally rearranged TCR-alpha beta transgenes (Tg-TCR) may influence thymocyte development by affecting the various selection events that control T cell differentiation. To gain insights into these processes, we have produced double transgenic animals carrying V(D)J recombination substrates in addition to the MHC class I (H-2Kb) allospecific KB5C20 Tg-TCR. We have analyzed substrate rearrangements in purified populations of Tg-TCR+ thymocytes in the situation of positive or negative selection. The profile of rearrangements found in SP thymocytes, positively selected for the Tg-TCR, suggests that expression of the KB5C20 Tg-TCR has only a minimal influence on substrate V(D)J recombination in cells differentiating along the major alpha beta T cell developmental pathway. In contrast, Tg-TCR+ DN thymocytes, in both positively and negatively selecting haplotypes, presented a profile that implies premature cessation of substrate rearrangements. This profile was maintained in peripheral Tg-TCR+ DN cells and was distinct from the one found in CD25+, alpha beta+, or gamma delta+ DN cells purified from mice transgenic for the recombination substrates only. These results are discussed with respect to the possible origin and differentiation pathway of Tg-TCR+ DN and SP cells.
Isolation of a developmental gene of Bacillus subtilis and its expression in Escherichia coli. (1983)

Glucose dehydrogenase of Bacillus subtilis is a developmental enzyme that is not found in growing (vegetative) cells but is synthesized after the differentiation process that leads to the production of endospores has started. We have isolated the gene coding for this enzyme from a lambda Charon 4A phage library of B. subtilis DNA. It is transcribed and translated in vegetative cells of the nondifferentiating organism Escherichia coli into enzymatically active glucose dehydrogenase that has the same physicochemical properties as the enzyme produced in B. subtilis during sporulation. Subcloning of the lambda DNA insert into pBR322 plasmid derivatives showed that the glucose dehydrogenase gene was transcribed in E. coli from a promoter within the B. subtilis genome.
The Economic Impact of Childhood Food Allergy in the United States (2013)

Childhood food allergy results in significant direct medical costs for the US health care system and even larger costs for families with a food-allergic child.
Employing an IL-23 p19 Vaccine to Block IL-23 Ameliorates Chronic Murine Colitis (2013)

IL-23 p19 vaccine is capable of downregulating inflammatory responses in chronic murine colitis, providing a novel therapeutic approach in Crohn's disease.
Effects of Selective Brain Cooling in Patients with Severe Traumatic Brain Injury: A Preliminary Study (2006)

We prospectively investigated non-invasive selective brain cooling (SBC) in patients with severe traumatic brain injury. Sixty-six in-patients were randomized into three groups. In one group, brain temperature was maintained at 33 - 35 degrees C by cooling the head and neck (SBC); in a second group, mild systemic hypothermia (MSH; rectal temperature 33 - 35 degrees C) was produced with a cooling blanket; and a control group was not exposed to hypothermia. Natural rewarming began after 3 days. Mean intracranial pressure 24, 48 or 72 h after injury was significantly lower in the SBC group than in the control group. Mean serum superoxide dismutase levels on Days 3 and 7 after injury in the SBC and MSH groups were significantly higher than in the control group. The percentage of patients with a good neurological outcome 2 years after injury was 72.7%, 57.1% and 34.8% in the SBC, MSH and control groups, respectively. Complications were managed without severe sequelae. Non-invasive SBC was safe and effective.
PatchMatch Stereo - Stereo Matching with Slanted Support Windows (2011)

Common local stereo methods match support windows at integer-valued disparities. The implicit assumption that pixels within the support region have constant disparity does not hold for slanted surfaces and leads to a bias towards reconstructing frontoparallel surfaces. This work overcomes this bias by estimating an individual 3D plane at each pixel onto which the support region is projected. The major challenge of this approach is to find a pixel’s optimal 3D plane among all possible planes whose number is infinite. We show that an ideal algorithm to solve this problem is PatchMatch [1] that we extend to find an approximate nearest neighbor according to a plane. In addition to Patch-Match’s spatial propagation scheme, we propose (1) view propagation where planes are propagated among left and right views of the stereo pair and (2) temporal propagation where planes are propagated from preceding and consecutive frames of a video when doing temporal stereo. Adaptive support weights are used in matching cost aggregation to improve results at disparity borders. We also show that our slanted support  windows can be used to compute a cost volume for global stereo methods, which allows for explicit treatment of occlusions and can handle large untextured regions. In the results we demonstrate that our method reconstructs highly slanted surfaces and achieves impressive disparity details with sub-pixel precision. In the Middlebury table, our method is currently top-performer among local methods and takes rank 2 among approximately 110 competitors if sub-pixel precision is considered.
Reagent and laboratory contamination can critically impact sequence-based microbiome analyses (2014)

These results suggest that caution should be advised when applying sequence-based techniques to the study of microbiota present in low biomass environments. Concurrent sequencing of negative control samples is strongly advised.
A Genomic Perspective on Protein Families (1997)

In order to extract the maximum amount of information from the rapidly accumulating genome sequences, all conserved genes need to be classified according to their homologous relationships. Comparison of proteins encoded in seven complete genomes from five major phylogenetic lineages and elucidation of consistent patterns of sequence similarities allowed the delineation of 720 clusters of orthologous groups (COGs). Each COG consists of individual orthologous proteins or orthologous sets of paralogs from at least three lineages. Orthologs typically have the same function, allowing transfer of functional information from one member to an entire COG. This relation automatically yields a number of functional predictions for poorly characterized genomes. The COGs comprise a framework for functional and evolutionary genome analysis.