gebhart/patrepeval huggingface dataset:
A review of 3-D packaging technology (1998)

This paper reviews the state-of-the-art in three-dimensional (3-D) packaging technology for very large scale integration (VLSI). A number of bare dice and multichip module (MCM) stacking technologies are emerging to meet the ever increasing demands for low power consumption, low weight and compact portable systems. Vertical interconnect techniques are reviewed in detail. Technical issues such as silicon efficiency, complexity, thermal management, interconnection density, speed, power etc. are critical in the choice of 3-D stacking technology, depending on the target application, and are briefly discussed.
Shape feature extraction from object corners (2002)

A method to extract shape features based on corners is described. Corners contain most of the shape information. Extraction of shape features which are invariant to scaling, rotation and translation is an important problem in computer vision and automatic target recognition systems. A Canny (1986) edge detector which is capable of producing single pixel wide edges is used for obtaining the contour from an image. Using this closed contour as input, the arch height function is computed at each point. The local maxima's correspond to the corner points in the shape. A set of efficient one dimensional moments which are invariant under rotation, translation and scale change is computed. These are the corresponding shape features. Classification is achieved by comparing the extracted features with the shape feature library. In order to validate the concept the following experiments were performed. Ten dissimilar aircrafts and ten similar aircrafts were used as inputs. Contour based moments performed better than the geometric moments in both the data sets. Rotation invariance of two very similar aircrafts showed that contour based moments performed better. The procedure described provides an elegant approach for extracting shape features. These features can also be used as inputs for training and recognizing shapes using neural networks.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Recent Advances in Topical Therapeutics for Vitreoretinal Diseases (2015)

Eye drops are convenient for patients, but achieving therapeutic doses and maintaining sustained drug release without frequent re-application to treat diseases of the retina has been largely unsuccessful. Topical administration of drugs is hindered by the anatomy, physiology, and biochemistry of the eye and its highly effective defence mechanisms. Advances in nanotechnology have led to the experimental use of topical permeation-enhancing liposomes, emulsions, and microspheres to enhance absorption and penetration of drugs across membranes; allow controlled release of the drug; and to target drugs at distinct tissues to allow sufficient local bioavailability. In the near future it is hoped that improved technologies may provide means of sustained topical drug delivery for retinal therapy, with improved side-effect profiles and reduced cost compared with currently available clinical treatments.
Immunological and clinical responses in metastatic renal cancer patients vaccinated with tumor RNA-transfected dendritic cells. (2003)

Autologous dendritic cells transfected with total renal tumor RNA have been shown to be potent stimulators of CTLs and antitumor immunity in vitro. A Phase I trial was conducted to evaluate this strategy for feasibility, safety, and efficacy to induce tumor-specific T-cell responses in subjects with metastatic renal cell carcinoma. Renal tumor RNA-transfected dendritic cells were administered to 10 evaluable study patients with no evidence of dose-limiting toxicity or vaccine-related adverse effects including autoimmunity. In six of seven evaluable subjects, expansion of tumor-specific T cells was detected after immunization. The vaccine-induced T-cell reactivities were directed against a broad set of renal tumor-associated antigens, including telomerase reverse transcriptase, G250, and oncofetal antigen, but not against self-antigens expressed by normal renal tissues. Although most patients underwent secondary therapies after vaccination, tumor-related mortality of the study subjects was unexpectedly low with only 3 of 10 patients dying from disease after a mean follow-up of 19.8 months. These data provide a scientific rationale for continued clinical investigation of this polyvalent vaccine strategy in the treatment of metastatic renal cell carcinoma and, potentially, other cancers.
Repertaxin, a novel inhibitor of rat CXCR2 function, inhibits inflammatory responses that follow intestinal ischaemia and reperfusion injury (2004)

1. Neutrophils are thought to play a major role in the mediation of reperfusion injury. CXC chemokines are known inducers of neutrophil recruitment. Here, we assessed the effects of Repertaxin, a novel low molecular weight inhibitor of human CXCL8 receptor activation, on the local, remote and systemic injuries following intestinal ischaemia and reperfusion (I/R) in the rat. 2. Pre-incubation of rat neutrophils with Repertaxin (10(-11)-10(-6) m) inhibited the chemotaxis of neutrophils induced by human CXCL8 or rat CINC-1, but not that induced by fMLP, PAF or LTB(4), in a concentration-dependent manner. Repertaxin also prevented CXCL8-induced calcium influx but not CXCL8 binding to purified rat neutrophils. 2. In a model of mild I/R injury (30 min of ischaemia and 30 min of reperfusion), Repertaxin dose-dependently (3-30 mg kg(-1)) inhibited the increase in vascular permeability and neutrophil influx. Maximal inhibition occurred at 30 mg kg(-1). 4. Following severe I/R injury (120 min of ischaemia and 120 min of reperfusion), Repertaxin (30 mg kg(-1)) markedly prevented neutrophil influx, the increase in vascular permeability both in the intestine and the lungs. Moreover, there was prevention of haemorrhage in the intestine of reperfused animals. 5. Repertaxin effectively suppressed the increase in tissue (intestine and lungs) and serum concentrations of TNF-alpha and the reperfusion-associated lethality. 6. For comparison, we also evaluated the effects of an anti-CINC-1 antibody in the model of severe I/R injury. Overall, the antibody effectively prevented tissue injury, systemic inflammation and lethality. However, the effects of the antibody were in general of lower magnitude than those of Repertaxin. 7. In conclusion, CINC-1 and possibly other CXC chemokines, acting on CXCR2, have an important role during I/R injury. Thus, drugs, such as Repertaxin, developed to block the function of the CXCR2 receptor may be effective at preventing reperfusion injury in relevant clinical situations.
Chitin and ChitosanValue-Added Products from Mushroom Waste (2004)

Accumulation of chitinous material in Agaricus bisporus stalks was determined during postharvest storage at 4 and 25 degrees C. The chitinous material was extracted after alkali treatment and acid reflux of alkali insoluble material and analyzed for yield, purity, degree of acetylation (DA), and crystallinity. The total glucosamine content in mushroom stalks increased from 7.14% dry weight (DW) at harvest (day 0) to 11.00% DW and 19.02% DW after 15 days of storage at 4 degrees C and 5 days of storage at 25 degrees C, respectively. The yield of crude chitin isolated from stalks stored at 25 degrees C for 5 days was 27.00% DW and consisted of 46.08% glucosamine and 20.94% neutral polysaccharides. The DA of fungal chitin was from 75.8 to 87.6%, which is similar to commercially available crustacean chitin. The yield of crude fungal chitin of 0.65-1.15% on a fresh basis indicates the potential for the utilization of these mushroom byproducts.
Live virus-free or die: coupling of antivirus immunity and programmed suicide or dormancy in prokaryotes (2012)

This article was reviewed by Arcady Mushegian, Etienne Joly and Nick Grishin. For complete reviews, go to the Reviewers' reports section.
Mitogen-activated Protein Kinase/ERK Kinase Kinases 2 and 3 Activate Nuclear Factor-κB through IκB Kinase-α and IκB Kinase-β (1999)

Recent evidence indicates that nuclear factor-kappaB (NF-kappaB), a transcription factor critically important for immune and inflammatory responses, is activated by a protein kinase cascade. The essential features of this cascade are that a mitogen-activated protein kinase kinase kinase (MAP3K) activates an IkappaB kinase (IKK) that site-specifically phosphorylates IkappaB. The IkappaB protein, which ordinarily sequesters NF-kappaB in the cytoplasm, is subsequently degraded by the ubiquitin-proteasome pathway, thereby allowing the nuclear translocation of NF-kappaB. Thus far, only two MAP3Ks, NIK and MEKK1, have been identified that can activate this pathway. We now show that MEKK2 and MEKK3 can in vivo activate IKK-alpha and IKK-beta, induce site-specific IkappaBalpha phosphorylation, and, relatively modestly, activate an NF-kappaB reporter gene. In addition, dominant negative versions of either IKK-alpha or IKK-beta abolish NF-kappaB activation induced by MEKK2 or MEKK3, thereby providing evidence that these IKKs mediate the NF-kappaB-inducing activities of these MEKKs. In contrast, other MAP3Ks, including MEKK4, ASK1, and MLK3, fail to show evidence of activation of the NF-kappaB pathway. We conclude that a distinct subset of MAP3Ks can activate NF-kappaB.
Controlling STI-related Parasitic Conduction in 90 nm CMOS and Below (2002)

In parallel to its continuous scaling, shallow trench isolation (STI) requires thorough optimisation with respect to its impact on device performance. In particular, the conduction occurring at the isolation edge of the device needs to be limited. Among the factors that influence the related control of threshold voltage and subthreshold current, this paper evaluates the impact of process parameters such as transistor architecture, trench profile (conventional or T-shape) and, for the first time, sacrificial oxidation strategy. It is first proven that conventional STI architecture can provide the same gate oxide integrity and control of lateral conduction as T-shape STI. Second, it is shown that transistor scaling improves immunity to narrow channel effects. This is illustrated with an optimised conventional STI module showing hump-free operation and threshold voltage variation of 40 mV down to 0.11 µm wide nMOS transistors, making the approach suitable at least down to the 90 nm technology node.
Nucleotide sequence of the Escherichia coli micA gene required for A/G-specific mismatch repair: identity of micA and mutY (1991)

The Escherichia coli methylation-independent repair pathway specific for A/G mismatches has been shown to require the gene product of micA. Extracts prepared from micA mutants do not form an A/G mismatch-specific DNA-protein complex and do not contain an A/G mismatch-specific nicking activity. Moreover, a partially purified protein fraction containing both A/G mismatch-specific nicking and binding activities restores repair activity in micA mutant extracts. The DNA sequence of a 2.3-kb fragment containing the micA gene has been determined. There are two open reading frames (ORF) in this DNA fragment: one ORF encodes a 25.7-kDa protein whose function is still unknown, the other ORF codes for a protein with an Mr of 39,147, but this ORF can be transcribed and the mRNA can be translated to yield a protein with an apparent Mr of 36 kDa on a sodium dodecyl sulfate-polyacrylamide gel. Deletion analysis showed that this 39.1-kDa ORF is the micA gene as judged by the capacity of the encoded protein to restore the A/G mismatch-specific nicking activity of micA mutant extracts. Furthermore, our results suggest that micA is the same gene as the closely mapped mutY, which encodes the A/G mismatch-specific glycosylase.
Clonal characterization of the human IgG antibody repertoire to Haemophilus influenzae type b polysaccharide. V. In vivo expression of individual antibody clones is dependent on Ig CH haplotypes and the categories of antigen. (1993)

Antibodies (Ab) to the polysaccharide capsule of Haemophilus influenzae type b (Hib-PS) provide protection against Haemophilus influenzae type b disease in children, and Hib-PS vaccines with different immunologic properties are widely used clinically. The repertoire of human anti-Hib-PS Ab induced by these vaccines is relatively restricted and can be divided into two types by the structure of the light chain V region. Ab using A2-V kappa II gene product, which account for the majority of anti-Hib-PS Ab response in most patients, show little somatic mutations. In contrast, non-Ab using A2-V kappa II gene product use VL genes from the V kappa I, V kappa II, V kappa III, V kappa IV, and V lambda subgroups, are variably expressed among patients, and contain somatic mutations. To further study the expression of these two types of anti-Hib-PS Ab, we have produced KB13, a mAb specific for V kappa II subgroup, and used mAb specific for various other VL subgroups to develop immunoassays specific for anti-Hib-PS Ab of each VL subgroup. When Ig allotypes were studied for the effect on the Ab repertoire, A2-V kappa II (A2) Ab were found to be expressed less in patients expressing fb or zag CH haplotypes (p < 0.05). When the T cell-independent Hib-PS carbohydrate vaccine was compared to two T cell-dependent Hib-PS protein conjugate vaccines for their effect on Ab repertoire, Ab using V kappa III VL were found to be more often elicited with the conjugate vaccines than with the Hib-PS carbohydrate vaccine (p < 0.01). Thus, individual members of the anti-Hib-PS Ab repertoire differ not only in their V region structure but also in the control of their expression.
S4‐04–05: Dimebon: A phase 3 investigational agent for Alzheimer's disease with a novel mitochondrial mechanism of action (2008)

Dimebon is an investigational oral small molecule currently in Phase 3 development for the treatment of Alzheimer's disease (AD). Dimebon is hypothesized to stabilize and enhance mitochondrial and neuronal function. Patients with mild-to-moderate AD treated with Dimebon for one year were stabilized on measures of cognition and memory, activities of daily living, behavior and global function, while placebo-treated patients declined significantly. The magnitude and durability of clinical benefits and excellent safety and tolerability profile observed for Dimebon in Alzheimer's patients suggests a mechanism of action (MOA) distinct from currently marketed AD drugs. Preclinical experiments confirm Dimebon's lack of significant activity against cholinesterases and NMDA receptors, consistent with its unique MOA. Similarly, Dimebon does not appear to interact with other targets implicated in cognition and memory, including the muscarinic receptors, nicotinic receptors and phosphodiesterases. Neurodegenerative diseases such as AD are characterized by synapse loss and neuron death. A body of literature suggests that abnormal depolarization of mitochondrial membranes plays a significant role in the loss of neuron function in several neurodegenerative diseases, including AD. Dimebon is a highly potent (pM to low nM) stabilizer of mitochondria as measured by JC-1 staining of primary neurons in culture. Dimebon is also a potent (pM to low nM) stimulator of neurite outgrowth in primary neurons derived from the cortex, hippocampus and spinal cord of rodents. Dimebon's neurotrophic effects are believed to be related to its ability to stabilize, protect and enhance mitochondrial and neuronal function. Dimebon's efficacy in animal models of memory impairment at picomolar plasma concentrations is consistent with a potent MOA. Neuroprotection measured by mitochondrial vital stains occurs within minutes to hours of Dimebon exposure, while the trophic effects on neurite outgrowth occur over longer exposures. These activities may be related to the short term and longer term effects of Dimebon seen in the completed pivotal Dimebon AD trial. Dimebon is a promising potential therapeutic agent for AD, with a unique and novel target, the mitochondria. The most potent activity of Dimebon identified to date is the stabilization and enhancement of mitochondrial and neuronal function.
Point-of-care diagnostics for noncommunicable diseases using synthetic urinary biomarkers and paper microfluidics (2014)

With noncommunicable diseases (NCDs) now constituting the majority of global mortality, there is a growing need for low-cost, noninvasive methods to diagnose and treat this class of diseases, especially in resource-limited settings. Molecular biomarkers combined with low-cost point-of-care assays constitute a potential solution for diagnosing NCDs, but the dearth of naturally occurring, predictive markers limits this approach. Here, we describe the design of exogenous agents that serve as synthetic biomarkers for NCDs by producing urinary signals that can be quantified by a companion paper test. These synthetic biomarkers are composed of nanoparticles conjugated to ligand-encoded reporters via protease-sensitive peptide substrates. Upon delivery, the nanoparticles passively target diseased sites, such as solid tumors or blood clots, where up-regulated proteases cleave the peptide substrates and release reporters that are cleared into urine. The reporters are engineered for detection by sandwich immunoassays, and we demonstrate their quantification directly from unmodified urine; furthermore, capture antibody specificity allows the probes to be multiplexed in vivo and quantified simultaneously by ELISA or paper lateral flow assay (LFA). We tailor synthetic biomarkers specific to colorectal cancer, a representative solid tumor, and thrombosis, a common cardiovascular disorder, and demonstrate urinary detection of these diseases in mouse models by paper diagnostic. Together, the LFA and injectable synthetic biomarkers, which could be tailored for multiple diseases, form a generalized diagnostic platform for NCDs that can be applied in almost any setting without expensive equipment or trained medical personnel.
Annual prevalence of diagnosed schizophrenia in the USA: a claims data analysis approach (2006)

Analyses of administrative claims data contribute to the understanding of the prevalence of diagnosed schizophrenia.
A unique mechanism regulating gene expression: translational inhibition by a complementary RNA transcript (micRNA). (1984)

The expression of the genes for the major outer membrane proteins OmpF and OmpC are osmoregulated. The ompC locus was found to be transcribed bidirectionally under conditions of high osmolarity and a 174-base transcript encoded upstream of ompC was found to inhibit the OmpF production and to substantially reduce the amount of the ompF mRNA. This RNA [mRNA-interfering complementary RNA (micRNA)] has a long sequence that is complementary to the 5' end region of the ompF mRNA. We propose that the micRNA inhibits the translation of the ompF mRNA by hybridizing with it. This RNA interaction may cause premature termination of the transcription of the ompF gene or destabilization of the ompF mRNA or both.
Assessment of Circulating Copy Number Variant Detection for Cancer Screening (2016)

ABSTRACT Current high-sensitivity cancer screening methods suffer from false positive rates that lead to numerous unnecessary procedures and questionable public health benefit overall. Detection of circulating tumor DNA (ctDNA) has the potential to transform cancer screening. Thus far, nearly all ctDNA studies have focused on detection of tumor-specific point mutations. However, ctDNA point mutation detection methods developed to date lack either the scope or sensitivity necessary to be useful for cancer screening, due to the extremely low (&lt;1%) ctDNA fraction derived from early stage tumors. We suggest that tumor-derived copy number variant (CNV) detection is theoretically a superior means of ctDNA-based cancer screening for many tumor types, given that, relative to point mutations, each individual tumor CNV contributes a much larger number of ctDNA fragments to the overall pool of circulating DNA. Here we perform an in silico assessment of the potential for ctDNA CNV-based cancer screening across many common cancers.
Immobilized metal affinity chromatography of DNA (1996)

Many of the most widely employed operations in molecular biology hinge upon the use of single-stranded DNA as a probe or template. Here we report a straightforward method by which to produce long single-stranded DNA molecules using the polymerase chain reaction (PCR) in combination with immobilized metal affinity chromatography (IMAC). We demonstrate that a tag consisting of six successive 6-histaminylpurine (H) residues (H6-tag) endows a DNA strand with selective retentivity onto a Ni2+-NTA-agarose chromatography matrix. The H6-tagged strand can then be eluted from the resin using 200 mM imidazole. Quantitative phosphorimaging analysis revealed that the PCR/IMAC procedure typically yields unmodified strands comprising >90% of the unbound DNA and H6-tagged strands comprising >95% of the bound fractions. DNA strands generated in this manner are shown to be excellent substrates for template-directed polymerization. The chemistry reported herein should facilitate a wide variety of operations in molecular biology, including automated DNA sequencing, hybridization screening of DNA libraries, assembly of gene cassettes, run-off transcription, site-directed mutagenesis and footprinting of protein-DNA complexes by template-directed interference footprinting.
Functional Analysis of Epidermal Growth Factor Receptor (EGFR) Mutations and Potential Implications for EGFR Targeted Therapy (2009)

EGFR mutations identified in NSCLC patients display distinct biological features. The variability in kinase activity, transforming potential, and sensitivity to EGFR inhibitors has to be considered in clinical studies aiming to correlate mutational status and drug response. The identification of comprehensive drug resistance profiles opens the opportunity to test alternative EGFR inhibitors in vitro.
[Proteinuria in diabetes mellitus]. (1988)

A third of all Type 1 diabetic patients will develop proteinuria as a clinical sign of diabetic nephropathy. A 100-fold increase in relative mortality is observed in patients with persistent proteinuria. Proteinuria is preceded by a microproteinuric phase, which is reversible upon optimized metabolic control. Thereby, progression towards clinically manifest nephropathy can be delayed. Macroproteinuria and progressive renal insufficiency are not influenced by metabolic control, but by aggressive antihypertensive therapy.
Adenovirus-mediated Hepatocyte Growth Factor Expression in Mouse Islets Improves Pancreatic Islet Transplant Performance and Reduces Beta Cell Death (2002)

Hepatocyte growth factor (HGF) increases beta cell proliferation and function in rat insulin promoter (RIP)-targeted transgenic mice. RIP-HGF mouse islets also function superiorly to normal islets in a transplant setting. Here, we aimed to determine whether viral gene transfer of the HGF gene into mouse islets ex vivo could enhance the performance of normal islets in a streptozotocin-diabetic severe combined immunodeficient mouse marginal islet mass model in which 300 uninfected or adenovirus (Adv) LacZ-transduced islet equivalents were insufficient to correct hyperglycemia. In dramatic contrast, 300 AdvHGF-transduced islet equivalents promptly (day 1) and significantly (p < 0.01) decreased random non-fasting blood glucose levels, from 351 +/- 20 mg/dl to an average of 191 +/- 7 mg/dl over 8 weeks. At day 1 post-transplant, beta cell death was significantly (p < 0.05) decreased, and the total insulin content was significantly (p < 0.05) increased in AdvHGF-transduced islets containing grafts. This anti-beta cell death action of HGF was independently confirmed in RIP-HGF mice and in INS-1 cells, both treated with streptozotocin. Activation of the phosphatidylinositol 3-kinase/Akt intracellular-signaling pathway appeared to be involved in this beta cell protective effect of HGF in vitro. In summary, adenoviral delivery of HGF to murine islets ex vivo improves islet transplant survival and blood glucose control in a subcapsular renal graft model in immuno-incompetent diabetic mice.