cssi/SciSciGPT-SciSciNet huggingface dataset:
Proteasome inhibitors shorten replicative life span and induce a senescent-like phenotype of human fibroblasts

The proteasome constitutes the main non-lysosomal cellular protease activity, and plays a crucial role not only in the disposal of unwanted material, but also in the regulation of numerous cellular processes. Previously, we have reported that during the replicative senescence of WI-38 fibroblasts there is a significant impairment in proteasome activity, which probably has important implications in the control of MAPK signaling and cellular proliferation. In this study, we report the potential role of the proteasome in the generation of the senescent phenotype in WI-38 fibroblasts. Our results indicate that inhibition of proteasome activity leads to an impairment in cell proliferation, and a shortening of the life span. The results also indicate that inhibition of the proteasome in young cells induces a premature senescent-like phenotype, as indicated by the increase in senescence-associated beta-galactosidase (SA beta-gal) activity and the abundance of both p21 and collagenase mRNAs, as well as a decreased level of EPC-1 mRNA known markers of cellular senescence, not previously shown to depend on proteasome activity. Together, our results suggest a molecular mechanism for the lack of responsiveness of human cells to growth factors, and point towards a role for the proteasome in the control of the life span of both cells and organisms.
Effect of Dietary Restriction on DNA-Adduct Formation of Benzo[a]pyrene and 2-Acetylaminofluorene in Mouse Liver

Abstract Dietary restriction (DR) alters hepatic drug metabolizing enzyme activities that affect the metabolic activation of xenobiotics. Previously, we have studied the effect of DR on the formation of benzo[a]pyrene (BaP)-DNA adducts in male Fischer 344 rats. In this study, the effects of DR on the formation of specific BaP-DNA adducts in mouse livers were investigated. In addition, 2-acetylaminofluorene (2-AAF) modified DNA adducts in livers of mice and rats were also examined. DR reduced the body and liver weights of male B6C3F1 mice. Both the total [3H]BaP-DNA binding and the specific BaP-DNA adduct, N2-dG-BaP, detected by 32P-postlabeling technique, were found to be greater in DR mice than in animals fed al libitum (AL). The formation of the 2-AAF-DNA adduct, AF-C8-dG, was not affected by DR. Similar results were obtained from the in vitro DNA adduct formation of these two carcinogens mediated by rat and mouse liver microsomes. The effect of DR on the formation of BaP- and 2-AAF-modified DNA adducts...
Psychosocial outcome in patients with moderate to severe head injury: 2-year follow-up

Psychosocial outcome and recovery of a group of 31 consecutive adult patients with moderate to severe head injuries were prospectively investigated over a 2-year period. A friend control group was used for comparison purposes. We conclude that moderate and severe head injuries have a significant long-term impact on psychosocial functioning. More specifically, although there is an increase over time in the number of subjects who resume former levels of activity, many moderate to severely head-injured people remain unable to work, support themselves financially, live independently and participate in pre-injury leisure activities at least up to 2 years post-injury. Initially, self-perceived limitations in everyday functioning are widespread, with physical functioning being of primary concern. Over time, there is improvement in both physical and psychosocial areas. However, in spite of improvement, difficulties in psychosocial functioning become dominant later due to greater improvement in the physical area. ...
The molecular basis of retinoic acid induced night blindness

Drugs which affect the processing of vitamin A in the retina or pigment epithelium can cause ocular toxicity. It is shown here that the retinoic acids, which are used in the treatment of skin disorders and which cause night blindness, inhibit the ocular retinol dehydrogenases in an in vitro system. This is shown to lead to a decrease in the formation of the visual chromophore 11-cis-retinal, thus explaining why night blindness might occur.
Sea-surface temperature anomalies associated with the 1997–1998 El Niño recorded in the oxygen isotope composition of planktonic foraminifera

Anomalously warm sea-surface temperatures and associated high rainfall propagated northward from the eastern equatorial Pacific along the western margin of North America during the 1997–1998 El Nino. We present data from the Guaymas Basin (Gulf of California) and the Santa Barbara Basin (Southern California Borderlands) that clearly demonstrate that the oxygen isotope composition of planktonic foraminifera accurately records the local sea-surface temperature changes related to the El Nino phenomenon. On the basis of this observation, the varved sediments accumulating in these basins should contain a detailed history of both the occurrence and intensity of past El Nino events.
Clinical Outcome of Henipavirus Infection in Hamsters Is Determined by the Route and Dose of Infection

Nipah virus (NiV) and Hendra virus (HeV) are emerging zoonotic viruses and the causative agents of severe respiratory disease and encephalitis in humans. Little is known about the mechanisms that govern the development of respiratory and neurological disease. Using a hamster model of lethal NiV and HeV infection, we describe the role of the route and dose of infection on the clinical outcome and determine virus tropism and host responses following infection. Infection of hamster with a high dose of NiV or HeV resulted in acute respiratory distress. NiV initially replicated in the upper respiratory tract epithelium, whereas HeV initiated infection primarily in the interstitium. In contrast, infection with a low dose of NiV or HeV resulted in the development of neurological signs and more systemic spread of the virus through involvement of the endothelium. The development of neurological signs coincided with disruption of the blood-brain barrier (BBB) and expression of tumor necrosis alpha (TNF-α) and interleukin 1 β (IL-1β). In addition, interferon-inducible protein 10 (IP-10) was identified as playing an important role in NiV and HeV pathogenesis. These studies reveal novel information on the development and progression of NiV and HeV clinical disease, provide a mechanism for the differences in transmission observed between NiV and HeV outbreaks, and identify specific cytokines and chemokines that serve as important targets for treatment.
The Normal D Region of the Ionosphere

The general theory of low-frequency sounding in the lower ionosphere is discussed in order to indicate the radio transmission characteristics which a D-layer model must satisfy. D layers based on the fundamental physical processes from 60 to 90 km, which have been presented up to now, have not been completely satisfactory. There is indication that the more accurately determined values of fundamental parameters now available, such as reaction rates, will lead to a more satisfactory model.
Chromophore Transformations in Red Fluorescent Proteins

The discovery of Anthozoa homologs of the green fluorescent protein (GFP) from jellyfish Aequorea victoria, which emit not only green but also yellow, orange, and red fluorescence, provided a powerful boost for in vivo labeling due to the colors and biochemical features never before encountered in GFP variants.1,2 GFP and several Anthozoa fluorescent proteins (FPs) have been developed into monomers suitable for protein tagging, such as: (i) permanently fluorescent conventional blue FP, yellow FPs, orange FPs, red FPs (RFPs), (ii) permanently fluorescent GFPs and RFPs with a large Stokes shift fluorescence emission (LSS-FPs), (iii) irreversibly photoactivatable/photoswitchable GFPs and RFPs,3,4 and (iv) fluorescent timers (FTs).5,6 Among various fluorescent probes, the most valuable for deep-tissue and whole-body imaging are the red-shifted FPs because of reduced autofluorescence, low light-scattering, and minimal absorbance at longer imaging wavelengths. The mechanisms of formation of the GFP-like chromophore and its transformations were studied and described very well, however only a few reviews of those for RFPs are available 2,7. Several mechanisms of the autocatalytic and photoinduced formation of the red chromophores have been proposed.7 Because of the complexity of the red chromophore transformations, no general integrating scheme has been suggested. Despite the numerous data available, there are long lasting contradictions about the formation of the red chromophore. From the discovery of a DsRed FP, the formation of a DsRed-like chromophore was commonly suggested to occur through a green GFP-like intermediate form,8 and only several recent publications uncovered that the formation of the DsRed-like chromophore occurs via a TagBFP-like blue intermediate form, not via the GFP-like one. More than 140 crystal structures are currently available for FPs of different classes, and some of them are for the same FP in a different state or containing different mutations. An overview of the structural data together with FP spectral and photochemical properties illustrate the relationship between the FPs’ structure and function. Here, we focus on a description of the chromophores in RFPs, suggest the mechanisms of the red chromophores formation and its further modifications, and attempt to discover general postulates for this complex chemistry. We also provide insights into how the red chromophore chemistry and the RFP crystal structures are translated into RFPs function. Lastly, we descuss major applications of RFPs in the modern imaging techniques.
Refractive radio scintillation in the solar wind

La radiosource extragalactique 3C279 a ete observee par VLA lorsque la source se trouvait a une elongation solaire de 0.9 o . Les resultats des observations montrent des variations lentes dans le flux, qui sont interpretees comme une scintillation de refraction causee par des heterogeneites de densite a grande echelle dans le vent solaire
Dynamics of Histone Tails within Chromatin

The physical and material properties of chromatin appear to influence gene expression by altering the accessibility of proteins to the DNA. The fundamental unit of chromatin, the nucleosome, consists of DNA wrapped around a core histone octamer protein. The tails of the histone proteins are flexible domains that are thought to play a role in regulating DNA accessibility and compaction; however the molecular mechanisms for these are not understood. using Site Directed Spin Labeling and Electron Paramagnetic Resonance (CW-EPR), we probe the dynamics of the histone tails within chromatin. The goal of this study is to further understand the function of histone tails and the part they play in gene regulation.
Periaqueductal gray matter dysfunction in migraine and chronic daily headache may be due to free radical damage

The periaqueductal gray matter (PAG) is at the center of a powerful descending antinociceptive neuronal network. We studied iron homeostasis in the PAG in episodic migraine patients between attacks and in chronic daily headache patients during headache using highresolution magnetic resonance imaging (MRI) techniques to map the transverse relaxation rates R2, R2* and R2’ in the PAG, red nucleus (RN) and substantia nigra (SN). R2’ is a measure of non–heme iron in tissues. We hypothesized that repeated hyperoxia of brainstem structures observed during migraine may generate free radical damage over time, resulting in iron deposition in vulnerable tissue. Seventeen patients diagnosed with episodic migraine with and without aura (EM), 17 with chronic daily headache (CDH) and medication overuse, and 17 normal adults (N) were imaged with a 3 tesla MRI system. In the PAG, there was a significant increase in mean R2’ and R2* values in both the EM and CDH groups (p<0.05) compared to normal, but no significant difference in these values between the EM and CDH groups, or between migraine with or without aura in the EM group. Positive correlations were found for duration of illness with R2’ in the EM and CDH groups. Duration of the episodic migraine stage in the CDH group did not correlate significantly with R2’, although the total duration of the episodic migraine plus daily headache stages of the CDH group strongly correlated with R2’. No effect of age was noted on R2’. Decrease in mean R2’ and R2* values also was observed in the RN and SN of the CDH compared to N and EM groups (p<0.05), explained best by flow activation due to head pain. Iron homeostasis in the PAG was selectively, persistently and progressively impaired in the EM and CDH groups, possibly caused by free radicals generated during repeated migraine attacks. These results support and emphasize the role of the PAG in migraine, potentially by dysfunctional control of the trigeminovascular nociceptive system. Development of CDH out of EM may be associated with a critical threshold of iron deposition and drug withdrawal excitation of the dysfunctional PAG.
NOTES FROM PRACTICE/UIT DIE PRAKTYK

I am an adoptive mother, and being a mother is one of the central aspects of my identity … I am not sure if there is a difference in identity between biological mother and adoptive mother, for I have not been a biological mother. What I do know is that my daughter and I share a bond and a love that would stand the test of time of any parent-child relationship. I have an equal faith that she is as unconditionally loved by her father, Paul, who risked breaking conventional stereotypes about masculinity in the way he cared for her – from clinic visits, changing diapers, bathing, dressing and feeding and carrying her on his back, and swaying her to sleep especially when the ugly pains of colic brought on uncontrollable crying. He was the constant in her life whenever my work required travelling. Yet it was a love that would be marred by fear as she grew up. If he could, he would have denied the biological parents out of existence – not out of vindictiveness, but for the sheer pain of loving in fear … and if it were left entirely up to him, he would have chosen not to tell at all.
Understanding Partial Statistics and Redundancy of Variables in Regression and Discriminant Analysis

Abstract Unexperienced users of statistical methods are sometimes confused by seeming contradictions between the results obtained by univariate variable-by-variable analyses and those obtained by multivariate methods. This article provides some teaching aids that I found useful for explaining the seemingly paradoxical situations to a mathematically untrained audience. Six typical situations are introduced in graphical form and supplemented with numerical examples, illustrating the notion of redundancy of variables and the meaning of partial statistics arising in multiple regression and discriminant analysis.
Sex-dependent effects of chronic unpredictable stress in the water maze

Exposure to chronic predictable stress, such as restraint, can affect performance on spatial memory tasks and these effects have been shown to be sex-specific in rats. It is not known whether unpredictable stress has similar sex-specific effects on spatial memory and whether those effects are present after the stress procedure has ended. Therefore, the current study tested male and female rats in the Morris water maze either immediately or 3 weeks following exposure to 10 days of unpredictable stress (CUS). Male and female rats were exposed to 10 days of stressors that varied by type and time of stressor application. Exposure to CUS decreased the distance swam to locate the hidden platform during acquisition training in the water maze for female but not male rats. Overall, male rats performed better than female rats during the acquisition, probe and matching to place trials. These effects were observed when assessing spatial memory performance immediately or 3 weeks following the last stressor. Plasma corticosterone levels followed the behavioral differences during the acquisition trials in that control female rats had increased basal and swim-stimulated corticosterone levels compared to CUS female rats and control male rats. These data demonstrate that unpredictable stress influences performance on the water maze in a sex-specific manner, which parallel plasma corticosterone levels. The improved performance of female rats following CUS exposure was present 3 weeks after the termination of the stress procedures, suggesting that stress may have lasting effects on underlying neural systems.
Expression of heat shock protein 60 in human proximal tubule cells exposed to heat, sodium arsenite and CdCl2

Abstract The expression of hsp 60 mRNA and protein were determined in human proximal tubule cells (HPT) exposed to lethal and sub-lethal concentrations of Cd 2+ under both acute and extended conditions of exposure. It was demonstrated that HPT cells exhibited the classic heat shock response when subjected to a physical (heat) or chemical stress (sodium arsenite). Heat stress, elevated temperature at 42.5°C for 1 h, caused an increase in both hsp 60 mRNA and protein following removal of the stress. Similar results were obtained when the cells were subjected to a classic chemical stress of exposure to 100 μM sodium arsenite for 4 h. Acute exposure of HPT cells to 53.4 μM CdCl 2 for 4 h also resulted in an increase in hsp 60 mRNA and protein following removal of the metal. An extended exposure to Cd 2+ was modeled by treating the cells continuously with Cd 2+ at both lethal and sub-lethal levels over a 16-day time course. It was demonstrated that chronic exposure to Cd 2+ failed to increase either hsp 60 mRNA or protein expression in HPT cells, even at concentrations of Cd 2+ that were lethal to the cells during the time course. In fact, hsp 60 protein levels were decreased compared to controls at lethal levels of Cd 2+ exposure. These findings suggest that hsp 60 expression may have two distinct roles when the human proximal tubule cell is exposed to Cd 2+ . A protective role through hsp 60 induction when the proximal tubule cell is acutely exposed to Cd 2+ and a deleterious role when hsp 60 protein is down-regulated during extended exposure to Cd 2+ .
The effect of stored blood on mesenteric oxygen extraction during exdotoxin shock.

Storage of blood in acid-citrate-dextrose (ACD) solution gradually depletes red cell 2,3-diphosphoglycerate (DPG) and increases the affinity of hemoglobin for oxygen. We examined the effect of exchange transfusion of DPG-depleted blood on mesenteric blood flow and oxygen consumption in dogs subjected to endotoxin shock. Two groups of 6 dogs each were anesthetized and subjected to exchange transfusion with either fresh ACD blood or 21-day-old ACD blood prior to administration ofEscherichia coli endotoxin (2 mg/kg). Mesenteric blood flow, arteriovenous oxygen content difference and systemic arterial blood pressure were monitored continuously before and for 60 min after endotoxin. Mesenteric blood flow was reduced from 250±21 ml/min before endotoxin to 114±15 ml/min at 5 min, 157±29 ml/min at 30 min, and 112±17 ml/min at 60 min after endotoxin in the dogs exchanged with fresh blood. Corresponding values for intestinal oxygen consumption were 10.4±1.0, 7.5±0.8, 8.4±1.0, and 6.8±0.7 ml/min. In dogs transfused with 21-day-old blood, pre-endotoxin blood flow was 208±2 ml/min and declined to 115±12, 93±5, and 80±8 ml/min at 5, 30, and 60 min post-endotoxin. Corresponding values for intestinal oxygen consumption were 8.1±0.9, 6.6±0.7, 6.2±0.5, and 5.5±0.7 ml/min. There was no significant difference (p>0.1) in responses of blood flow or oxygen consumption to endotoxin shock between the two groups of dogs. These findings indicate that exchange transfusion with DPG-depleted blood does not impair oxygen extraction by the ischemic intestine.
Frequency and causes of overanticoagulation and underanticoagulation in patients treated with warfarin

Study Objective. To determine the frequency and the specific causes of over-and underanticoagulation in patients who receive warfarin therapy and are managed in an anticoagulation clinic. Design. Retrospective medical record review. Setting. University-affiliated anticoagulation clinic. Subjects. One thousand twenty patients (mean age 60.2 yrs [range 17–84 yrs]) receiving warfarin therapy during a 1-year index period. Measurements and Main Results. Of 12,897 international normalized ratios (INRs) evaluated, 6642 (51.5%) were within range and 8525 (66.1%) were within 0.2 INR units of range. Among 2881 out-of-range INRs below 2.0, the most common cause of underanticoagulation was indeterminate (856, 29.7%). Response to previous change in dosage (16.4%), noncompliance or dosing errors (16.3%), and initiation of therapy (15.6%) were other common causes of underanticoagulation. Changes in drugs, medical condition, dietary vitamin K intake, alcohol use, and activity level, in combination, accounted for only 15.1% of INRs below 2.0. Among 603 out-of-range INRs greater than 4.0, the most common cause of overanticoagulation was indeterminate (43.0%). Changes in medical condition (15.9%), response to a previous change in warfarin dosage (11.4%), and interactions with prescription drugs (7.3%) were other common causes of overanticoagulation. In combination, noncompliance or dosing errors, initiation of therapy, and change in dietary vitamin K intake accounted for only 15.4% of INR values above 4.0. Conclusion. Out-of-range INRs are encountered frequently during warfarin therapy as a result of changes in numerous factors. Despite extensive evaluation of potential causes of over- and underanticoagulation, a specific cause commonly cannot be determined.
Doppler and acceleration tolerances of high-gain, wideband linear FM correlation sonars

An analysis is presented of the decorrelation effects of target velocity and acceleration on high-gain, wideband linear FM correlation sonars that match the received signal against a family of velocity reference functions, each of which is a different time-compressed or -expanded replica of the transmitted signal. Such sonars are shown to have velocity (i.e., Doppler) and acceleration tolerances far different from that predicted by narrowband radar theory. Unlike the narrowband case, the wideband velocity tolerance may be quite small and is approximately independent of the carrier frequency and inversely proportional to the time-bandwidth product (TW). Narrowband radar-type calculations of velocity tolerance can give erroneous results far in excess of the true value. This is because the narrowband velocity tolerance is derived entirely on the basis of temporal overlap loss, whereas the actual tolerance depends primarily on the slope difference between the frequency-time sweeps of the received and reference signals. High acceleration tolerance, without separate acceleration processing channels, can be achieved by cross-correlating the acceleration return with a "best match" velocity reference function. The resultant wideband acceleration tolerance is approximately inversely proportional to WT2and better than the narrowband tolerance by a factor of 12 Q (Q = carrier frequency/bandwidth). This improvement arises because the wideband reference functions are able to partially compensate for the nonlinearity imparted to the transmitted frequency-time sweep by an accelerating target, whereas such compensation is not possible in narrowband systems employing carrier-shifted reference functions.
An odor discrimination model with application to kin recognition in social insects.

The problem of discriminating between a number of similar, nonspecific odors is discussed with special reference to the phenomenon of kin and nestmate discrimination in social insects. Guided by the basic physiological and anatomical features of the olfactory sensory receptors and neural pathways in insects, a model is presented for the process of odor discrimination. The model hypothesizes neural processing capabilities that include the logarithmic transformations of electrical potentials to generate a scalar quantity representing the “similarity” of two multivalued signals. The model thereby quantifies the notion of phenotype matching that appears in the kin recognition literature, and makes the concept of a recognition template more precise. The hypotheses underlying the model suggest a number of neurophysiological studies that should be undertaken, while the model itself provides a hasis lor integrating several areas of research pertaining to kin recognition in particular species of animals.
Role of Human Cytomegalovirus Immediate-Early Proteins in Cell Growth Control

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that has been implicated in several disorders, including an association between HCMV reactivation and the overproliferation of arterial smooth muscle cells observed in restenosis. Although HCMV can mediate a growth-arrest phenotype in infected cells, the virus can also promote an environment conducive to proliferation. Here, we present evidence that the HCMV immediate-early (IE) proteins, IE1-72 and IE2-86, may be responsible for inducing this proliferative environment by altering cell cycle control. We find that expression of either of these IE proteins can alter the cell cycle distribution of randomly cycling cells towards S and G(2)/M phases. Additionally, we find that expression of IE2-86, but not IE1-72, induces quiescent cells into S phase and delays cell cycle exit. In the absence of p53, IE1-72 expression can induce S phase and delay cell cycle exit. We also demonstrate that p53 protein levels increase in fibroblasts following the expression of IE1-72. The observed accumulation of p53 protein in IE1-72-expressing cells may account for the inability of IE1-72 to induce S phase and delay cell cycle exit. Our data suggest that expression of HCMV IE1-72 and IE2-86 is sufficient to alter the cell cycle to generate an environment conducive to proliferation.
Spread of human cancer cells occurs with probabilities indicative of a nongenetic mechanism

There has been much uncertainty as to whether metastasis requires mutation at the time of spread. Here, we use clinical data to calculate the probability of the spread of melanoma and breast cancer cells. These calculations reveal that the probability of the spread of cancer cells is relatively high for small tumours (∼1 event of spread for every 500 cells for melanomas of 0.1 mm) and declines as tumours increase in size (∼1 event of spread for every 108 cells for melanomas of 12 mm). The probability of spread of breast cancer cells from the lymph nodes to the periphery is ∼1 event of spread for every 108 cells in the nodal masses, which have a mean diameter of 5 mm, while the probability of spread of cancer cells from the breast to the periphery when the primary masses are 5 mm is also ∼1 event of spread for every 108 cells. Thus, the occurrence of an event of spread from the breast to the lymph nodes appears not to increase the propensity of the progeny of those cells to spread from the lymph nodes to the periphery. These values indicate that the spread of human breast cancer and melanoma cells is unlikely to occur by a mechanism requiring mutation at the time of spread.
A haptic system for a multifingered hand

A series of haptic exploratory procedures (EPs) implemented for a multifingered, articulated, sensory robot hand is discussed. These EPs are designed to extract specific tactile and kinesthetic information from an object via their purposive invocation by an intelligent robotic system. Taken together, they form an active robotic touch perception system. This system utilizes a PUMA 560 robot arm, a JPL/Stanford robot hand with joint torque sensing in the fingers, a wrist force/torque sensor, and a 256-element spatially resolved fingertip tactile array. The EPs are described, and experimental results are given. >
EFFECTS OF HALOTHANE AND OTHER VOLATILE ANAESTHETICS ON PROTEIN SYNTHESIS AND SECRETION IN GUINEAPIG LIVER SLICES

SUMMARY We have investigated the effect of volatile anaesthetics on protein synthesis and secretion in Hartley male guineapig liver slices. The slices (250–300 μm thick) were incubated in sealed roller vials containing Krebs-Henseleit buffer at 37°C under 95% oxygen. Volatile anaesthetics were vaporized in the vials to produce constant concentrations in the medium. Halothane 1–2.1 mmol litre−1 produced a concentration-related decrease in protein synthesis (3H-leucine incorporation) and secretion. Deuter-ated halothane (d-halothane), which is less bio-transformed, was less inhibiting than halothane: uptake of the 3H-leucine was not affected but its incorporation into the nascent peptide was inhibited. Enflurane 2.2 mmol litre−1, isoflurane 2.2 mmol litre−1 and sevoflurane 2.1 mmol litre−1 also inhibited protein synthesis, but to a lesser extent than halothane and d-halothane. We conclude that alterations in protein synthesis and secretion are an early and sensitive indicator of cellular injury by volatile anaesthetics in liver slices.
The Fate of Stars in the Vicinity of Supermassive Black Holes

When a star approaches the neighborhood of a supermassive black hole, the tidal forces acting on the star trigger a vast range of physical effects that could yield unique observational signatures. Of particular interest are ultraclose passages of stars by massive black holes. These encounters could not only unveil general relativistic effects but also provide favorable conditions for the detonation of the star. This article presents a general review of the tidal stellar disruption phenomenon.
Vaccinating against zoonotic parasitic diseases: myth or reality?

The largely unanticipated difficulties of parasite vaccine development have led us to a renewed awareness of the survival strategies evolutionarily embedded within parasites over hundreds of millions of years. We have grown to appreciate that efforts to disrupt parasite–host relationships are substantially compounded by our incomplete understanding of the complex immune responses that occur in the naturally infected host. Given the inability to transfer laboratory successes to field trials, research is leading us to conclude that genetically defined animal models may not be good predictors of the unique and disparate protective immune responses one can expect from the genetically heterogeneous populations of animals that represent the parasite's natural environment. This is further compounded by the abundance of mechanisms parasites have created for themselves to defend against immune intervention. Thus, in the never-ending saga of vaccine development, it is only appropriate that pitfalls and advancements be critiqued as they apply across parasite groups, with a look towards promising technologies that may propel this field to the level of scientific achievement once envisaged.
Transcriptional Compensation for Gene Loss Plays a Minor Role in Maintaining Genetic Robustness in Saccharomyces cerevisiae

If a gene is mutated and its function lost, are compensatory genes upregulated? We investigated whether genes are transcriptionally upregulated when their synthetic sick or lethal (SSL) partners are lost. We identified several new examples; however, remarkably few SSL pairs exhibited this phenomenon, suggesting that transcriptional compensation by SSL partners is a rare mechanism for maintaining genetic robustness.
Antibacterial Bioagents Based on Principles of Bacteriophage Biology: An Overview

Bacteriophages were discovered almost a century ago. With the advent of antibiotics, the use of bacteriophages for treatment of infections fell out of favor in Western medicine. In light of the rise of antibiotic resistance, phages and their products (lysins) are rediscovered as antibacterial bioagents. This overview summarizes principles of phage biology and their translation for therapeutic and preventive applications. Examples are presented to highlight their therapeutic promise for prophylaxis and treatment of bacterial infections including multidrug-resistant organisms in humans and animals, and their use as decontaminants of food supplies and environments. Besides research on the in vivo behavior of phages and lysins, dialogues between researchers and regulatory agencies are necessary to publish guidelines for bacteriophage manufacturing and formulation for human use. Only well-designed, double-blind randomized controlled trials will determine if phages and lysins are safe and effective adjuncts or alternatives to antibiotic therapy for infections with multidrug-resistant organisms.
Role of dynein, dynactin, and CLIP-170 interactions in LIS1 kinetochore function

Mutations in the human LIS1 gene cause type I lissencephaly, a severe brain developmental disease involving gross disorganization of cortical neurons. In lower eukaryotes, LIS1 participates in cytoplasmic dynein-mediated nuclear migration. We previously reported that mammalian LIS1 functions in cell division and coimmunoprecipitates with cytoplasmic dynein and dynactin. We also localized LIS1 to the cell cortex and kinetochores of mitotic cells, known sites of dynein action. We now find that the COOH-terminal WD repeat region of LIS1 is sufficient for kinetochore targeting. Overexpression of this domain or full-length LIS1 displaces CLIP-170 from this site without affecting dynein and other kinetochore markers. The NH2-terminal self-association domain of LIS1 displaces endogenous LIS1 from the kinetochore, with no effect on CLIP-170, dynein, and dynactin. Displacement of the latter proteins by dynamitin overexpression, however, removes LIS1, suggesting that LIS1 binds to the kinetochore through the motor protein complexes and may interact with them directly. We find that of 12 distinct dynein and dynactin subunits, the dynein heavy and intermediate chains, as well as dynamitin, interact with the WD repeat region of LIS1 in coexpression/coimmunoprecipitation and two-hybrid assays. Within the heavy chain, interactions are with the first AAA repeat, a site strongly implicated in motor function, and the NH2-terminal cargo-binding region. Together, our data suggest a novel role for LIS1 in mediating CLIP-170–dynein interactions and in coordinating dynein cargo-binding and motor activities.
Issues interfering with the use of written communication as a means of relational bonding between absentee, divorced fathers and their children

Abstract Using a nationwide sample, this study surveyed divorced, absentee fathers about issues that interfere with effective written communication that might be used as a means of relational bonding. The findings indicate that uncertainty about the father's parental role contributes to feelings of writing apprehension and feelings of writing competence. Parental role uncertainty was also negatively correlated with predicting the child's behavior, trust and disclosure by the father. Discussions of the these issues are presented along with recommendations for workshops to improve writing skills for divorced, absentee parents.
Fabrication of Long Length Thin Walled Liners for Use in Compression Physics Experiments

Summary form only given. The focus of this poster is to explain the fabrication techniques and tooling used to produce long length thin walled liners used in a series of high energy density experiments. The long length thin walled liner is used in spallation experiments and acts as the driver converging onto the target. The combination of very thin wall (3 mm) over the length of (234 mm) caused manufacturing issues, such as concentricity and surface finish. Fixturing, tooling and operational methods controlled the vibrations which affect the accuracy and taper of the finished liner.
A diagnostic marker for speech delay associated with otitis media with effusion: the intelligibility-speech gap.

The goal of this study was to determine if notably reduced intelligibility is a potential diagnostic marker for children with speech delay and histories of early recurrent otitis media with effusion (SD‐OME). Intelligibility was assessed in one 5–10 minute conversational speech sample from each of 281 speakers. The OME histories of 148 of these children with normal speech acquisition were described in two prior reports. OME histories of 85 additional children with speech delay were obtained from case history reports. For both groups, the children with positive OME (OME+) histories had significantly lower intelligibility scores but significantly higher speech production scores than children with negative OME (OME−) histories. Findings for a diagnostic marker to discriminate speech delayed children with OME+ versus OME− histories were promising, considering that the data were obtained retrospectively and did not include audiological information characterizing children's concurrent fluctuant hearing loss. Th...
Gene order phylogeny and the evolution of methanogens.

Methanogens are a phylogenetically diverse group belonging to Euryarchaeota. Previously, phylogenetic approaches using large datasets revealed that methanogens can be grouped into two classes, “Class I” and “Class II”. However, some deep relationships were not resolved. For instance, the monophyly of “Class I” methanogens, which consist of Methanopyrales, Methanobacteriales and Methanococcales, is disputable due to weak statistical support. In this study, we use MSOAR to identify common orthologous genes from eight methanogen species and a Thermococcale species (outgroup), and apply GRAPPA and FastME to compute distance-based gene order phylogeny. The gene order phylogeny supports two classes of methanogens, but it differs from the original classification of methanogens by placing Methanopyrales and Methanobacteriales together with Methanosarcinales in Class II rather than with Methanococcales. This study suggests a new classification scheme for methanogens. In addition, it indicates that gene order phylogeny can complement traditional sequence-based methods in addressing taxonomic questions for deep relationships.
In their own words: Trauma and substance abuse in the lives of formerly homeless women with serious mental illness

In-depth interviews were conducted with 13 formerly homeless mentally ill women to capture their individual life trajectories of mental illness, substance abuse, and trauma in their own words. Cross-case analyses produced 5 themes: (a) betrayals of trust, (b) graphic or gratuitous nature of traumatic events, (c) anxiety about leaving their immediate surroundings (including attending group treatment programs), (d) desire for one's own space, and (e) gender-related status loss and stigmatization. Findings suggest formerly homeless mentally ill women need (and want) autonomy, protection from further victimization, and assistance in restoring status and devalued identity. Avenues for intervention include enhanced provider training, addressing experiences of betrayal and trauma, and more focused attention to current symptoms rather than previous diagnoses.
Antibodies possessing multiple antigen specificities and exhibiting extensive idiotypic cross-reactivity.

The specificity of the interaction between the combining site (paratope) of an antibody molecule and an antigenic determinant (epitope) is a concept originated from the first immunochemical studies conducted at the beginning of the century by von Behring and Arrhenius [ 11. This concept is a paradigm for all theories aimed at explaining the function of the immune system [2,3]. X-ray crystallographic studies of the association between an antibody molecule and an antigenic determinant allowed a molecular approach of the understanding of this interaction. These studies showed that only a few contacting residues borne by the hypervariable regions of the V regions interact with the functional groups of the epitope [4]. These studies determined that the binding of a hapten to an antibody is based on a structural complementarity with minimal structural adaptation, since only a few residues of the hypervariable region and a few functional groups of the antigen are involved in antigen-antibody interactions. It was believed from these experiments that each antibody would be specific for a single possible antigen. However, there are studies showing that antibodies can bind to several non cross-reactive antigens [5]. These studies followed the development of the hybridoma technology since the availability of monoclonal antibodies provided tools to determine the binding of the same paratope to several antigenic determinants. Examples of multi-specificity
Effective Specific Impulse of External Nuclear Pulse Propulsion Systems

An investigation of a simple self-similar flow model for an external nuclear pulse propulsion system indicates that to achieve the high effective specific impulse of such a system three principal factors are required. The are (1) attaining pulses of optimum energy, (2) attaining good propellant collimation, and (3) using an ablative material for the pusher surface which has high absorptivity for radiant energy at the propellant stagnation temperature.
On the performance of episodic UWB and direct-sequence communication systems

We consider a binary pulsed communication system, with possibly episodic transmission, i.e., the system transmits n pulses per information bit and allows for off-time separation between pulses. In the ultra-wideband (UWB) regime, such systems are motivated for overlay applications, as well as low probability of intercept and low probability of detection scenarios. Processing gain enables low-power transmission, and the UWB pulsing limits the interference effects into narrowband systems. We introduce a random ternary sequence model and use this to study multiuser system performance. We consider the issues of processing gain, jamming margin, coding gain, and multiuser interference (MUI) for a single-user matched filter receiver. The introduction of episodic transmission, with a corresponding reduction in bit rate, provides system flexibility with respect to both MUI rejection and handling multipath channels. Highly episodic transmission provides nearly orthogonal low-rate users, even with system asynchrony and no power control. Performance of a single-user RAKE receiver is evaluated via a Chernoff bound on bit error rate, in the presence of MUI. The analysis includes the impact of fading as well as pilot-aided channel estimation.
Pipeline interleaved programmable DSP's: Architecture

Programmable processors specialized to intensive numerical computation and real-time signal processing are often deeply pipelined. The ensuing gain in throughput is moderated by the difficulty of efficiently programming such processors. Techniques for overcoming this difficulty are effective only for modest amounts of pipelining. This paper proposes applying an old but rarely used architectural approach to the design of single-chip signal processors so that the potential benefits of extensive pipelining can be fully realized. The architectural approach is to interleave multiple processes (or programs) through a single deeply pipelined processor in such a way that the disadvantages of deep pipelining disappear. Instead, the user is faced with the need to construct programs that can execute as concurrent processes. The main advantage is that much more pipelining can be used without aggravating the programming. A specific experimental architecture is outlined. The solution offered is a "system solution" in that architectural performance is considered along with programmability and ease of use. In the companion paper, data flow programming is suggested so that algorithms can be automatically partitioned for concurrent execution. Data flow provides a natural environment in which to build signal processing programs and can be supported efficiently in an architecture of the type described here.
Two novel schemes for truncating finite element meshes

In this paper, we investigate two mesh truncation schemes for finite element method (FEM) simulations. Specifically, we examine the performance of a new anisotropic perfectly matching layer and a numerical boundary condition (NBC) for truncating standard and printed guided structures. Results will be presented for modeling propagation in metallic waveguides and shielded microstrip lines.
Measured Pressure Distribution and Local Heat Transfer Rates for Flow Over Concave Hemispheres

The use of parachutes for recovery of equipment from very high velocity vehicles, such as missiles, has directed attention to the need for aerodynamic and heat transfer information associated with such high drag bodies. With this application in mind, a solid concave hemisphere, positioned in a subsonic flow, was studied. Plexiglas models were placed in water and in air streams, and by using straightforward flow visualization techniques it was determined that the flow in the cup was, in essence, a separate flow region. Quantitative measurements were made of the pressure distribu­ tion and local heat transfer rate over a Reynolds number range of 6000 to 89,000. The pressure on the inner surface of the hemisphere was found to be equal to the total pressure from the stagnation point to an angle of 75 deg, dropping somewhat at greater angles. The heat transfer was found to increase monotonically from the stagnation point to the edge. The overall dimensionless heat transfer may be given in the form NuD/(ReD)^2 = 0.42. R ECENT interest in the use of parachutes for the re­ covery of equipment from high speed vehicles has di­ rected attention to the aerodynamics and heat transfer of extremely high drag bodies. At the time the present study of heat transfer to parachutes was initiated, only limited aerodynamic information was available, and no pertinent heat transfer information was found in the open literature. [Recently, information on the pressure distribution about a hemisphere with 20 per cent porosity (l)3 and heat transfer data for a fist-type parachute (2) has become available.] To obtain preliminary estimates of the time-temperature history of descending parachutes, the porosity was neglected and the convective heat transfer coefficients were estimated for an upstream facing hemisphere. The convective coeffi­ cient on the rear surface was assumed to be the same as on the rear surface of a sphere. For the front surface of the hemisphere, the potential flow solution of Schiffman and Spencer (3) yielded the velocity and pressure distribution, which, in turn, was used to determine the local convective heat transfer performance. The velocity and heat transfer results are shown in Fig. 1 and compared with established values for flow over the front side of a sphere; surprisingly, the predicted velocity and heat transfer coefficient distribu­ tion for the front face of the hemisphere is very similar to the distribution on the front face of a sphere. However, the validity of these results was brought sharply into question when preliminary pressure distribution measurements using a solid hemisphere gave markedly different behavior. As a consequence, a rather detailed aerodynamic and heat transfer investigation using concave hemispheres was initiated.