Miracle-dz/UniFAR-FTUs huggingface dataset:
RIP1 suppresses innate immune necrotic as well as apoptotic cell death during mammalian parturition

Significance The protein kinase receptor interacting protein 1 controls signaling via death receptors, Toll-like receptors, and retinoic acid-inducible gene 1-like receptors, dictating inflammatory outcomes as broad as cytokine activation and cell death. RIP1 makes a vital contribution during development, evident from the fact that RIP1-deficient mice die soon after birth. Here, we show that a kinase-independent function of RIP1 dampens the consequences of innate immune cell death. During parturition, RIP1 prevents the lethal consequences of RIP3-dependent necroptosis as well as caspase 8 (Casp8)-dependent apoptosis. In contrast to the RIP1-deficient phenotype, mice lacking a combination of RIP1, RIP3, and Casp8 are born and mature into viable, fertile, and immunocompetent adults. These results demonstrate the important protective role of RIP1 against physiologic and microbial death cues encountered at birth. The pronecrotic kinase, receptor interacting protein (RIP1, also called RIPK1) mediates programmed necrosis and, together with its partner, RIP3 (RIPK3), drives midgestational death of caspase 8 (Casp8)-deficient embryos. RIP1 controls a second vital step in mammalian development immediately after birth, the mechanism of which remains unresolved. Rip1−/− mice display perinatal lethality, accompanied by gross immune system abnormalities. Here we show that RIP1 K45A (kinase dead) knockin mice develop normally into adulthood, indicating that development does not require RIP1 kinase activity. In the face of complete RIP1 deficiency, cells develop sensitivity to RIP3-mixed lineage kinase domain-like–mediated necroptosis as well as to Casp8-mediated apoptosis activated by diverse innate immune stimuli (e.g., TNF, IFN, double-stranded RNA). When either RIP3 or Casp8 is disrupted in combination with RIP1, the resulting double knockout mice exhibit slightly prolonged survival over RIP1-deficient animals. Surprisingly, triple knockout mice with combined RIP1, RIP3, and Casp8 deficiency develop into viable and fertile adults, with the capacity to produce normal levels of myeloid and lymphoid lineage cells. Despite the combined deficiency, these mice sustain a functional immune system that responds robustly to viral challenge. A single allele of Rip3 is tolerated in Rip1−/−Casp8−/−Rip3+/− mice, contrasting the need to eliminate both alleles of either Rip1 or Rip3 to rescue midgestational death of Casp8-deficient mice. These observations reveal a vital kinase-independent role for RIP1 in preventing pronecrotic as well as proapoptotic signaling events associated with life-threatening innate immune activation at the time of mammalian parturition.
Does language lateralization depend on the hippocampus?

Children acquire language even in the presence of extensive damage to classical left‐hemisphere language areas. Moreover, following acute brain lesions, children recover lost language functions much better than adults (Vargha‐Khadem et al ., 1994). One reason for the superior recovery in children is a greater capability for functional reorganization, the most striking example being the shifting of language from the damaged to the intact hemisphere. Transhemispheric reorganization is an intriguing mechanism because it seems to allow the reinstatement of language by the recruitment of a homologous neural circuitry in the unaffected hemisphere. Considerable reorganization, including transhemispheric shifting of language in response to brain lesions, can also occur in adults (Weiller et al ., 1995). The degree of recovery in adults is highly variable. One reason may be that humans differ in the extent of hemispheric specialization and, as a consequence, in their capability to transhemispherically compensate for unilateral disturbances (Knecht et al ., 2002). While in adults transhemispheric compensation seems to be rare, in children it is more common. In this issue of Brain , Liegeois and her colleagues report on the neural reorganization of the language system …
IMMUNOGLOBULIN LEVELS DURING CHILDHOOD, WITH SPECIAL REGARD TO IgE

In a series comprising 215 children of ages 2–15 years, representative of the population in a medium‐sized Swedish town, determinations were made of the 5 immunoglobulins IgG, IgA, IgM, IgD and IgE. The children were divided with regard to the occurrence of allergic symptoms and to their general state of health. The results were subjected to extensive statistical calculations including regression analyses with regard to age and sex for the different immunoglobulins. A longitudinal study of the IgE development during the first year of life was also carried out.
Donor insemination – historical background and current developments

Donor insemination (DI) was shrouded in secrecy for many years.The majority of doctors recommended parents not to disclose their use of DI neither to their child nor to friends or family members. In the last two decades, this secrecy has increasingly been challenged.This article outlines the historical background and discusses the current legal and professional regulations. Furthermore, it summarizes scientific knowledge regarding the development of children conceived by DI and provides the reader with our current understanding of the implications of DI on family dynamics. It also illustrates the donors’ motivations and attitudes and concludes by highlighting the need for psychosocial counselling prior to treatment.
A simple nonlinear model for the optical recording channel

This study is concerned with the development of a simple yet sufficiently accurate model for the replay signal in optical discs. A method is proposed which models data storage (the write channel) as a nonlinear process and data retrieval (the read channel) as a linear one. The result is a low-complexity nonlinear model, of which the linear binary-PAM model is a special case. The performance of the proposed model is demonstrated by application to experimentally measured DVD data, and is found to be both accurate as well as robust to different recording media and conditions.
ENDOPHTHALMITIS AFTER INTRAVITREAL ANTI–VASCULAR ENDOTHELIAL GROWTH FACTOR ANTAGONISTS: A Six-Year Experience at a University Referral Center

Purpose: To assess the rate of infectious endophthalmitis and to describe the clinical and microbiological features of eyes that develop clinically suspected endophthalmitis after an intravitreal injection of vascular endothelial growth factor antagonists. Methods: The medical records of patients undergoing intravitreal injections of anti-vascular endothelial growth factor agents from January 1, 2005, through December 31, 2010, at a single university referral center and associated satellite clinics were retrospectively analyzed to determine the rate of infectious endophthalmitis after intravitreal anti-vascular endothelial growth factor injections. Results: Twelve cases (11 patients) of clinically suspected endophthalmitis were identified after a total of 60,322 injections (0.02%; 95% confidence interval, 0.0114%-0.0348%). Of the 12 cases, 11 presented within 3 days of the injection. Of the 7 culture-positive cases, 5 were because of Streptococcus species. In 4 of the 5 Streptococcus cases, final visual acuity was hand motions or worse. The rate of clinically suspected endophthalmitis was 0.018% after bevacizumab and 0.027% after ranibizumab injections. Conclusion: A very low rate of endophthalmitis after intravitreal injections of anti-vascular endothelial growth factor agents was observed. Patients typically presented within 3 days of injection. Streptococcus species was the most common bacteria isolated, and it was generally associated with poor visual outcomes.
Formal definition and dating of the GSSP (Global Stratotype Section and Point) for the base of the Holocene using the Greenland NGRIP ice core, and selected auxiliary records

The Greenland ice core from NorthGRIP (NGRIP) contains a proxy climate record across the Pleistocene–Holocene boundary of unprecedented clarity and resolution. Analysis of an array of physical and chemical parameters within the ice enables the base of the Holocene, as reflected in the first signs of climatic warming at the end of the Younger Dryas/Greenland Stadial 1 cold phase, to be located with a high degree of precision. This climatic event is most clearly reflected in an abrupt shift in deuterium excess values, accompanied by more gradual changes in δ18O, dust concentration, a range of chemical species, and annual layer thickness. A timescale based on multi‐parameter annual layer counting provides an age of 11 700 calendar yr b2 k (before AD 2000) for the base of the Holocene, with a maximum counting error of 99 yr. A proposal that an archived core from this unique sequence should constitute the Global Stratotype Section and Point (GSSP) for the base of the Holocene Series/Epoch (Quaternary System/Period) has been ratified by the International Union of Geological Sciences. Five auxiliary stratotypes for the Pleistocene–Holocene boundary have also been recognised. Copyright © 2008 John Wiley & Sons, Ltd.
Sensitivity of the Pediatric Early Warning Score to Identify Patient Deterioration

OBJECTIVE: We evaluated the Pediatric Early Warning Score (PEWS) sensitivity as an early indicator of patients deterioration leading to a Rapid Response Team (RRT)/code event. We hypothesized that at least 80% of patients had a critical PEWS preceding the event. We determined staff awareness of deterioration in patient status prior to the event as evidenced by consults, addition of monitoring equipment or increased frequency of assessment. The timing of these events was compared to critical PEWS times. METHODS: One hundred and seventy non-ICU RRT and 16 code events were identified between October 2006 and February 2008. We completed retrospective PEWS at four-hour intervals or less for twenty-four hours preceding the event. The PEWS algorithm, guiding staff to consult at a critical score ≥4 or a single domain score equal to 3, was applied. RESULTS: For 85.5% of patients the earliest indicator of deterioration, evidenced by a critical PEWS, was a median of 11 hours 36 minutes and the earliest preceding the event was 30 minutes. For 97.1% of patients the earliest median time to a consult was 80 minutes. Oximetry was added 6.9 hours for 43.5% of patients. 7% of patients had increased nursing assessment. A sub-group of patients had 1) critical PEWS, 2) consult and 3) addition of a monitor. The median time for earliest critical PEWS for these was significant (P < 0.001). CONCLUSION: PEWS can potentially provide a forewarning time >11 hours, alerting the team to adapt the care plan and possibly averting an RRT or code.
Seller Strategies for Differentiation in Highly Competitive Online Auction Markets

We explore the issue of seller differentiation in competitive auction environments, where most sellers have a high percentage of positive feedback. Analyzing a set of eBay auction listings for identical products, we find evidence that the use of visibility-enhancing and quality-signaling discretionary auction attributes affects auction outcomes throughout the auction process (i.e., listing views, bids, and price premiums). We also find strong evidence that the number of reputable sellers in an auction marketplace moderates the effects of these discretionary attributes on auction outcomes. Specifically, as auction environments become more competitive, these attributes become more effective tools for differentiation, whereas seller feedback scores become less effective. Furthermore, sellers appear to select their strategies for employing these discretionary attributes based on both their prior experience and the number of experienced reputable sellers in the market. These findings suggest that in addition to relying on feedback scores, online sellers must take a more strategic approach in the selection of discretionary attributes in their auction listings.
Utility of Inoculum Counting (Walshe and English Criteria) in Clinical Diagnosis of Onychomycosis Caused by Nondermatophytic Filamentous Fungi

ABSTRACT Opportunistic onychomycosis caused by nondermatophytic molds may differ in treatment from tinea unguium. Confirmed diagnosis of opportunistic onychomycosis classically requires more than one laboratory analysis to show consistency of fungal outgrowth. Walshe and English in 1966 proposed to extract sufficient diagnostic information from a single patient consultation by counting the number of nail fragments positive for inoculum of the suspected fungus. Twenty fragments were plated per patient, and each case in which five or more fragments grew the same mold was considered an infection by that mold, provided that compatible filaments were also seen invading the nail tissue by direct microscopy. This widely used and often recommended method has never been validated. Therefore, the validity of substituting any technique based on inoculum counting for conventional follow-up study in the diagnosis of opportunistic onychomycosis was investigated. Sampling of 473 patients was performed repeatedly. Nail specimens were examined by direct microscopy, and 15 pieces were plated on standard growth media. After 3 weeks, outgrowing dermatophytes were recorded, and pieces growing any nondermatophyte mold were counted. Patients returned on two to eight additional occasions over a 1- to 3-year period for similar examinations. Onychomycosis was etiologically classified based on long-term study. Opportunistic onychomycosis was definitively established for 86 patients. Counts of nondermatophyte molds in initial examinations were analyzed to determine if they successfully predicted both true cases of opportunistic onychomycosis and cases of insignificant mold contamination. There was a strong positive statistical association between mold colony counts and true opportunistic onychomycosis. Logistic regression analysis, however, determined that even the highest counts predicted true cases of opportunistic onychomycosis only 89.7% of the time. The counting criterion suggested by Walshe and English was correct only 23.2% of the time. Acremonium infections were especially likely to be correctly predicted by inoculum counting. Inoculum counting could be used to indicate a need for repeat studies in cases of false-negative results from laboratory direct microscopy. Inoculum counting cannot serve as a valid substitute for follow-up study in the diagnosis of opportunistic onychomycosis. It may, nonetheless, provide useful information both to the physician and to the laboratory, and it may be especially valuable when the patient does not present for follow-up sampling.
Can We Use Biomarkers and Functional Assays to Implement Personalized Therapies in Transplantation?

Research in transplantation focuses on minimizing immunosuppression to decrease side effects and costs. Indeed, in some patients, partial or complete cessation of immunosuppression is successful, but currently we have no means of identifying suitable patients a priori. Current withdrawal protocols, which do not implement surrogate markers, carry a significant risk of graft injury. To minimize the risk, immune monitoring strategies are required. Here, we review recently described biomarkers and assays, which might enable identification of patients suitable for partial or complete weaning and patients at risk of rejection. The predictive power of these parameters has to be tested in prospective multicenter trials.
OBSERVATIONS ON THE INFLUENZA EPIDEMIC IN THE BRISTOL GENERAL HOSPITAL

of M1ilitary Cases. -Io Mray, 7; axersge strengtil of tro-ops 1,30. In Jue, 5; strength 700. In July, 6; pneumonia 1; streugth 490. In August, 3; strength 500, In September, none. In October, 11; pneumonia 4; strength 650. In November, 13; pneLlmonia 7-; relapses 2; effusions 2; strength 600. In December, & streptonocc; tAnToats2; strength 1,008. Total military cases treated 130. Pneuemonla 12; relapsea 8; atreptococea Lhrnat2.2:; deaths0.
The chaperonin TRiC forms an oligomeric complex in the malaria parasite cytosol

The malaria parasite exports numerous proteins into its host red blood cell (RBC). The trafficking of these exported effectors is complex. Proteins are first routed through the secretory system, into the parasitophorous vacuole (PV), a membranous compartment enclosing the parasite. Proteins are then translocated across the PV membrane in a process requiring ATP and unfolding. Once in the RBC compartment the exported proteins are then refolded and further trafficked to their final localizations. Chaperones are important in the unfolding and refolding processes. Recently, it was suggested that the parasite TRiC chaperonin complex is exported, and that it is involved in trafficking of exported effectors. Using a parasite‐specific antibody and epitope‐tagged transgenic parasites we could observe no export of Plasmodium TRiC into the RBC. We tested the importance of the parasite TRiC by creating a regulatable knockdown line of the TRiC‐θ subunit. Loss of the parasite TRiC‐θ led to a severe growth defect in asexual development, but did not alter protein export into the RBC. These observations indicate that the TRiC proteins play a critical role in parasite biology, though their function, within the parasite, appears unrelated to protein trafficking in the RBC compartment.
Predominant Bacteria in an Activated Sludge Reactor for the Degradation of Cutting Fluids

For the first time, an activated sludge reactor, established for the degradation of cutting fluids, was examined for predominant bacteria. In addition, both total and viable numbers of bacteria in the reactor were determined so that the percentage of each predominant type in the total reactor population could be determined. Three samples were studied, and a total of 15 genera were detected. In each sample, the genus Pseudomonas and the genus Microcyclus were present in high numbers. Three other genera, Acinetobacter, Alcaligenes, and Corynebacterium, were also found in every sample but in lower numbers. In one sample, numerous appendaged bacteria were present, and one of these, the genus Seliberia, was the most predominant organism in that sample. However, in the other two samples no appendaged bacteria were detected. Six genera were found in this reactor which have not been previously reported in either cutting fluids in use or in other activated sludge systems. These genera were Aeromonas, Hyphomonas, Listeria, Microcyclus, Moraxella, and Spirosoma. None of the predominant bacteria belonged to groups of strict pathogens.
Chemokines and cancer

The chemokines and their receptors are a superfamily of small secreted molecules that control the migration of many cell types in the body. Several years ago it became clear that some chemokines and receptors regulate the migration of certain cells in the lymphoid system, and this raised the possibility that chemokines could also control the migration of tumor cells in the body. Breast cancer cells were found to express chemokine receptors in a nonrandom manner, and these observations pointed to several chemokine/receptor pairs that control tumor‐cell migration. The most important ligand/receptors pairs in these phenomena include CXCL12/CXCR4 and CCL21/CCR7. Since then, there has been intense interest in this area and many studies have been published, especially on CXCR4. These studies point to the following conclusions: (i) Tumors express chemokine receptors in a nonrandom manner. (ii) CXCR4 is the most widely expressed chemokine receptor in many different cancers. (iii) CCR7 is also expressed by many cancers, and is likely to mediate metastasis to the lymph nodes in selected cancers. (iv) The effects of CXCL12 on CXCR4‐bearing tumor cells likely include many other functions (growth, differentiation) besides migration. During normal development, the interaction CXCL12/CXCR4 is known to be involved in organogenesis. This process shares many characteristics with metastasis, and represents one of the key areas of future research. © 2006 Wiley‐Liss, Inc.
A highly linear and efficient differential CMOS power amplifier with harmonic control

A 2.45 GHz fully differential CMOS power amplifier (PA) with high efficiency and linearity is presented. For this work, a 0.18-/spl mu/m standard CMOS process with Cu-metal is employed and all components of the two-stage circuit except an output transformer and a few bond wires are integrated into one chip. To improve the linearity, an optimum gate bias is applied for the cancellation of the nonlinear harmonic generated by g/sub m3/ and a new harmonic termination technique at the common source node is adopted along with normal harmonic termination at the drain. The harmonic termination at the source effectively suppresses the second harmonic generated from the input and output. The amplifier delivers a 20.5dBm of P/sub 1dB/ with 17.5 dB of power gain and 37% of power-added efficiency (PAE). Linearity measurements from a two-tone test show that the power amplifier with the second harmonic termination improves the IMD3 and IMD5 over the amplifier without the harmonic termination by maximally 6 dB and 7 dB, respectively. Furthermore, the linearity improvements appear over a wide range of the power levels and the linearity is maintained under -45 dBc of IMD3 and -57dBc of IMD5 when the output power is backed off by more than 5dB from P/sub 1dB/. From the OFDM signal test, the second harmonic termination improves the error vector magnitude (EVM) by over 40% for an output power level satisfying the 4.6% EVM specification.
Suture-Endobutton Fixation of Ankle Tibio-Fibular Diastasis: A Cadaver Study

Suture-Endobutton fixation is proposed as a minimally invasive, flexible fixation of ankle tibio-fibular diastasis, which would not require routine removal. This study tested the Suture-Endobutton construct in a cadaver syndesmosis injury model and compared this against A.O. syndesmosis screw fixation. Sixteen embalmed cadaver legs were used. Phase one consisted of placing the leg in a jig, generating an external rotation torque and measuring diastasis with increasing intraosseous membrane division. Phase two then compared the Suture-Endobutton construct vs. single four-cortex 4.5 mm A.O. screw fixation. Diastasis increased significantly with increasing intraosseous membrane division (p<0.001). No significant differences were seen in the mean rate of failure between the Suture-Endobutton and A.O. screw fixation. However, the Suture-Endobutton did give a significantly more consistent performance; the distribution of standard deviations for A.O. screw fixation was 0.64 mm higher than that for the Endobutton (95% C.I. 0.46 to 0.84). These results show that Suture-Endobutton fixation at least equals the performance of screw fixation and encourages clinical trials in ankle injuries with a syndesmosis diastasis.
Scaffold Design and Manufacturing: From Concept to Clinic

Since Robert Langer and colleagues pioneered the concept of reconstructing tissue using cells transplanted on synthetic polymer matrices in the early 1990s, research in the field of tissue engineering and regenerative medicine has exploded. This is especially true in the development of new materials and structures that serve as scaffolds for tissue reconstruction. The basic tenet of the last two decades holds scaffolds as degradable materials providing temporary function while enhancing tissue regeneration through the delivery of biologics. Although a number of new scaffolding materials and structures have been developed in research laboratories, the application of such materials practice even has been extremely limited. This paper argues that better integration of all these factors is needed to bring scaffolds from “concept to clinic”. It reviews current work in all these areas and suggests where future work and funding is needed.